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T Kodama

Publications and source records attributed to T Kodama.

At least 127 records · Page 7Linked to original sources
PubMed2000

Role of macrophage scavenger receptor in endotoxin shock.

Lipopolysaccharide (LPS) is known to bind to several receptors on macrophages, including CD14 and macrophage scavenger receptor class A types I and II (MSR-A), and stimulates macrophages to release various inflammatory mediators. MSR-A recognizes a broad range of polyanionic ligands such as chemically modified lipoproteins, LPS of Gram-negative bacteria, and lipoteichoic acid of Gram-positive bacteria, suggesting a role in host defence. In this study, mice lacking MSR-A were used to elucidate the role of MSR-A in endotoxin shock. Peritoneal macrophages from MSR-A-deficient (MSR-A(-/-)) mice bound less remarkably to LPS than those from wild-type (MSR-A(+/+)) mice and the binding activity of MSR-A(+/+) macrophages to LPS was reduced by the addition of an anti-MSR-A antibody. Clearance of LPS in serum was retarded in MSR-A(-/-) mice after intraperitoneal administration of LPS. LPS-induced expression of cytokines in the liver was similar in MSR-A(+/+) and MSR-A(-/-) mice, but levels of interleukin (IL)-1beta expression and serum IL-1beta were lower in MSR-A(-/-) mice. Administration of large doses of LPS resulted in a higher mortality of MSR-A(+/+) mice and pretreatment with an IL-1 receptor antagonist reduced the mortality. Thus, MSR-A-mediated macrophage activation plays a negative role in protecting mice from endotoxin shock by enhancing IL-1beta production by macrophages.

Animals↗
PubMed2000

Onion-bulb formation after a single compression injury in the macrophage scavenger receptor knockout mice.

Onion-bulb (OB) formation is often encountered in acquired neuropathies such as chronic inflammatory demyelinating polyradiculoneuropathy and diabetic neuropathy and is believed to require repeated injuries to peripheral nerves. Although this suggests that remaining damaged cell membranes, including myelin debris, might trigger OB formation, the molecular mechanism remains unclear. In this study, we were successful in producing many small OBs after a single compression injury to peripheral nerves of the knockout mice deficient of macrophage scavenger receptor class A (MSR-A). Although morphometry showed no difference in the average densities of the remaining myelinating fibers between wild-type and MSR-A knockout mice after the compression injury, there were more macrophages and myelin debris positive for oxidized-phosphatidylcholine in the nerves from the MSR-A knockout mice. We believe that OB formation was induced after a single compression injury as the result of delayed phagocytosis of myelin debris possessing oxidized lipids by MSR-A deficient macrophages. The present work shed light on the molecular mechanism of OB formation seen in chronic neuropathies and provided a model for further investigation.

Animals↗
PubMed2000

Molecular cloning and DNA analysis of the orotidine-5'-phosphate decarboxylase gene from the yeast Saccharomyces exiguus Yp74L-3.

The orotidine-5'-phosphate decarboxylase gene of Saccharomyces exiguus Yp74L-3 was cloned as a DNA fragment complementing a ura4 mutation of this yeast. The coding region of the gene is 807 bp in length, and represents 68.7% similarity to the corresponding gene of S. cerevisiae (URA3). The cloned URA4 gene was shown to be located on the 790-kbp Chromosome (chr) VIII of S. exiguus Yp74L-3. The neighbor-joining phylogenetic tree based on the orotidine-5'-phosphate decarboxylase coding sequences indicates that S. exiguus Yp74L-3 is closely related to Kluyveromyces yeasts, as well as to a S. cerevisiae laboratory strain.

Chromosome Mapping↗
PubMed2000

Successful surgical treatment for implanted intraperitoneal metastases of hepatocellular carcinoma.

We report here two patients with hepatocellular carcinoma who experienced implanted metastases in the abdominal cavity after hepatectomy or microwave coagulo-necrotic therapy. Hepatic resection and microwave coagulo-necrotic therapy were successful for these tumors, and the postoperative status was satisfactory in both patients. Implanted metastases were discovered in the abdominal cavity of each of these two patients 6 months after surgery. It is necessary to look not only for the presence of liver metastasis but also for the recurrence of the tumor in the abdominal cavity during the follow-up period. Generally, surgical resection for intraabdominal implanted tumors arising from any other abdominal organs is not indicated for improving the patient's quality of life. However, resection of metastatic tumors that occur in the abdominal cavity, arising from hepatocellular carcinoma may be of value in improving patient survival.

Aged↗
PubMed2000

Genomic structure of the gene encoding human 3-hydroxy-3-methyl-glutaryl coenzyme A reductase: comparison of exon/intron organization of sterol-sensing domains among four related genes.

We determined the genomic structure of the human gene encoding 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which catalyzes the conversion of HMG-CoA to mevalonate and is the rate-limiting and major regulatory enzyme in sterol biosynthesis. The gene is more than 21 kb long, about five times the size of its corresponding cDNA. It consists of 20 exons, ranging in size from 68 to 1809bp. An amino-terminal hydrophobic membrane-bound domain is encoded by exons 2-10, a flexible linker domain by exons 10 and 11, and the catalytic domain by exons 11-20. Exons 3-7 encode a sterol-sensing domain. We compared its genomic structure in this region with the sterol-sensing domains of three related genes, sterol regulatory element binding protein (SREBP) cleavage-activating protein (SCAP), Niemann-Pick type C1 protein (NPC1), and a morphogen receptor, Patched. Two of the five positions of introns in the sterol-sensing domain of the HMG-CoA reductase gene were identical to the exon/intron organization of this domain in the related human genes, but these positions of introns were not conserved in homologues from lower organisms, except in one instance. The data suggested that exon-shuffling may have occurred during relatively recent evolution: this would account for the structural similarity of this domain in four quite different human proteins.

Amino Acid Sequence↗
PubMed2000

Genomic structure and chromosomal mapping of the human site-1 protease (S1P) gene.

Site-1 protease (S1P) is a subtilisin-related enzyme that cleaves sterol regulatory element-binding proteins (SREBPs) in the lumen of endoplasmic reticulum, thereby initiating the release of transcriptionally active NH2-terminal fragments of SREBPs from membranes. In the experiments reported here, we localized the human S1P gene to chromosome 16q24 by fluorescent in situ hybridization and radiation-hybrid mapping, and determined its genomic structure. This gene is more than 60 kb long and contains 23 exons and 22 introns. Its transcription-initiation site within exon 1 is separate from the initiation codon in exon 2. Analysis of the exon/intron structure revealed that the S1P gene consists of a mosaic of functional units: exon 1 encodes the 5' non-translated region; exon 2 encodes the NH2-terminal signal sequence; and exons 2 and 3 encode the pro-peptide sequence that is released when S1P is self-activated by intramolecular cleavage. Exons 5-10 encode the subtilisin-homology domain that is critical for catalytic activity, and exon 23 encodes the transmembrane region. Analysis of the putative promoter region revealed a highly G/C-rich region containing a binding site for ADD1/SREBP-1, as well as Sp1 and AP2 sites. Therefore, expression of the S1P gene may be under the control of SREBP-1, a key regulator of the expression of genes essential for intracellular lipid metabolism. Our data establish a basis for investigations to detect molecular variants in this gene that may alter levels of plasma lipoproteins and/or otherwise disrupt intracellular lipid metabolism.

Base Sequence↗
PubMed2000

Cytoplasmic molecular delivery with shock waves: importance of impulse.

Cell permeabilization using shock waves may be a way of introducing macromolecules and small polar molecules into the cytoplasm, and may have applications in gene therapy and anticancer drug delivery. The pressure profile of a shock wave indicates its energy content, and shock-wave propagation in tissue is associated with cellular displacement, leading to the development of cell deformation. In the present study, three different shock-wave sources were investigated; argon fluoride excimer laser, ruby laser, and shock tube. The duration of the pressure pulse of the shock tube was 100 times longer than the lasers. The uptake of two fluorophores, calcein (molecular weight: 622) and fluorescein isothiocyanate-dextran (molecular weight: 71,600), into HL-60 human promyelocytic leukemia cells was investigated. The intracellular fluorescence was measured by a spectrofluorometer, and the cells were examined by confocal fluorescence microscopy. A single shock wave generated by the shock tube delivered both fluorophores into approximately 50% of the cells (p < 0.01), whereas shock waves from the lasers did not. The cell survival fraction was >0.95. Confocal microscopy showed that, in the case of calcein, there was a uniform fluorescence throughout the cell, whereas, in the case of FITC-dextran, the fluorescence was sometimes in the nucleus and at other times not. We conclude that the impulse of the shock wave (i.e., the pressure integrated over time), rather than the peak pressure, was a dominant factor for causing fluorophore uptake into living cells, and that shock waves might have changed the permeability of the nuclear membrane and transferred molecules directly into the nucleus.

Biophysical Phenomena↗
PubMed2000

Endoscopic mucosal resection using a partial transparent hood for lesions located tangentially to the endoscope.

BACKGROUND: Numerous methods have been developed to resect early-stage gastric and esophageal cancers, but it is difficult to resect lesions viewed tangentially with the endoscope. METHODS: We have designed and developed an original method of endoscopic mucosal resection using a partial transparent hood to treat difficult cases in which the lesions are located tangentially to the endoscope. The hood was attached on the right side of the endoscope and, after insertion into the stomach or the esophagus, was lightly pressed on the orad side of the lesion. Then the lesion was resected using grasping forceps and electrosurgical current snare. RESULTS: The average diameter of specimens was 26 +/- 8 mm in gastric lesions and 20 +/- 3 mm in esophageal lesions, both 6 mm larger than those obtained by previous methods. CONCLUSION: This device and technique were extremely useful for mucosal resection of lesions located tangentially to the endoscope.

Electrosurgery↗
PubMed2000

IL-18 deficiency selectively enhances allergen-induced eosinophilia in mice.

BACKGROUND: T(H2) cytokines are associated with airway inflammation and hyperreactivity in bronchial asthma, and restoration of the T(H1)/T(H2) imbalance is a potential avenue for novel therapies. IL-18 is a cytokine secreted by activated macrophages, and it shares some of its biologic activities with IL-12, a typical T(H1)-type cytokine. Although IL-18 and IL-12 act on T cells synergistically to induce IFN-gamma production, the contribution of IL-18 T(H1)/T(H2) imbalance and to subsequent asthmatic response has not been elucidated in vivo. OBJECTIVE: We studied a model of allergic asthma in IL-18-deficient mice to investigate the modulatory role of IL-18 on induction and maintenance of T(H2) mucosal immunity. We also have investigated the ability of intraperitoneal instilled IL-18 to reduce T(H2) mucosal immunity in IL-18-deficient mice. METHODS: IL-18-deficient mice immunized to ovalbumin by means of intraperitoneal injection were challenged 3 times with an aerosol of ovalbumin every second day for 8 days. Recombinant (r)IL-18 was intraperitoneally administered in mice before every first challenge. Mice were analyzed for effects on lung eosinophilia, cytokines, and serum IgE levels. RESULTS: In IL-18-deficient mice, levels of eosinophilia and lung damage were significantly higher than in wild-type C57/BL6 litter mates. Intraperitoneal administration of rIL-18 in deficient mice reduced these antigen-induced changes to levels seen in wild-type mice in association with a decrease in IL-4 in bronchoalveolar lavage fluid and lung tissue. However, administration of rIL-18 did not affect the IFN-gamma level and somewhat enhanced the production of IL-5. Notably, reconstitution with rIL-18 increased the numbers of cells staining for Fas ligand, as well as apoptotic cells stained by nick end-labeling in bronchial submucosa infiltrates. CONCLUSION: These findings indicate that in vivo IL-18 not only inhibited antigen-specific T(H2) development but also affected apoptosis through Fas-Fas ligand interactions. These data support a role for IL-18 in the complex pathogenesis of allergic inflammation in which IL-18 limited the development of the local inflammatory response to antigen.

Allergens↗
PubMed2000

Significance of serum pro-gastrin-releasing peptide as a predictor of relapse of small cell lung cancer: comparative evaluation with neuron-specific enolase and carcinoembryonic antigen.

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) have been reported to be useful markers for staging, monitoring treatment, and predicting relapse in patients with small cell lung cancer (SCLC). Recently, pro-gastrin-releasing peptide (Pro-GRP) became available as a sensitive, specific, and reliable tumor marker for patients with SCLC. The aim of this study is to determine the most useful tumor marker to detect the relapse of SCLC. Furthermore, we analyzed the relationship between tumor markers at relapse and survival from relapse or response to salvage chemotherapy. Medical records were reviewed to obtain serum levels of Pro-GRP, NSE, and CEA before and after the initial chemotherapy, and at relapse. Consecutive 66 patients with SCLC, with an objective response and confirmed relapse treated at the National Cancer Center Hospital East, were analyzed in this study. The percentages of patients whose tumor marker level were elevated before treatment, decreased after the treatment, and increased again at relapse were 67% (95% CI, 55-78) for Pro-GRP, 20% (10-29) for NSE, and 38% (26-50) for CEA. Multivariate analysis indicated that poor performance status before initial treatment and elevated serum levels of lactate dehydrogenase at relapse were poor prognostic factors for patients with recurrent SCLC (P<0.005). None of the serum levels of Pro-GRP, NSE, and CEA at relapse was a significant prognostic factor and associated with an objective response to salvage chemotherapy. The present study demonstrated that serum levels of Pro-GRP reflect the disease course of patients with SCLC most accurately.

Aged↗
PubMed2000

Disappearance of nodular mesangial lesions in a patient with light chain nephropathy after long-term chemotherapy.

A 64-year-old man developed multiple myeloma (kappa light chain type), nephrotic syndrome, and renal insufficiency in 1993. A renal biopsy showed typical histological findings of light chain nephropathy: nodular glomerulosclerosis with deposition of kappa light chains in the mesangial area and subendothelial space of the glomerular capillary walls. Long-term intermittent MEVP chemotherapy (melphalan, 4 mg/d for 4 days; cyclophosphamide, 100 mg/d for 4 days; vincristine, 1 mg/d; prednisolone, 40 mg/d for 4 days) diminished proteinuria and improved renal function. In April 1999, a follow-up biopsy showed remarkable diminution of nodular lesions and disappearance of kappa light chain deposits. Although the prognosis of light chain nephropathy has been considered poor, long-term successful chemotherapy can clear light chain deposits and restore renal function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Implication of dopaminergic mechanisms in the wake-promoting effects of amphetamine: a study of D- and L-derivatives in canine narcolepsy.

Using a canine model of narcolepsy and selective DA and NE uptake inhibitors, we have recently shown that DA uptake inhibition promotes wakefulness, while NE uptake inhibition inhibits rapid eye movement sleep and cataplexy. In order to further delineate the respective roles of the dopaminergic and noradrenergic systems in the pharmacological control of symptoms of narcolepsy, we compared the potency of amphetamine isomers (D- and L-amphetamines) and a derivative (L-methamphetamine) on wakefulness and cataplexy. Their respective effects on these narcolepsy symptoms were then compared with their in vivo effects on extracellular DA levels in the caudate and NE levels in the frontal cortex during local drug perfusion in narcoleptic dogs. Polygraphic recordings demonstrated that D-amphetamine was about twice as potent as L-amphetamine, and was six times more potent than L-methamphetamine in increasing wakefulness and reducing slow-wave sleep. D-Amphetamine and L-amphetamine were equipotent in reducing rapid eye movement sleep and cataplexy, and L-methamphetamine was about half as potent as L- and D-amphetamines. D-Amphetamine was found to be more potent in increasing DA efflux than L-amphetamine, and L-methamphetamine was found to have little effect on DA efflux; there was no significant difference in the potencies of the three derivatives on NE efflux. The potencies of these amphetamines on wakefulness correlated well with DA, but not NE, efflux in the brain of narcoleptic dogs during local drug perfusion. Our current results further exemplify the importance of the DA system for the pharmacological control of electroencephalogram arousal and suggest that increased DA transmission mediates the wake-promoting effects of amphetamine-like stimulants.

Amphetamine↗
PubMed2000

Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries.

The predominant H. pylori strain circulating among geographic locations differs with regard to the genomic structure. This study determined whether structural subtypes of the cagA 3' repeat region could be used to identify the population of origin of H. pylori isolates. We examined 600 cagA-positive H. pylori (Colombia, 100; USA, 100; France, 100; Canada, 20; Italy, 20; Korea, 100; Japan, 100; Hong Kong, 20; Taiwan, 20; Vietnam, 20). The cagA 3' region was amplified by PCR using primers specific to Japanese and Western 3' cagA gene sequences. PCR using Japanese cagA primers resulted in PCR products in 99-6 % of strains from East Asia but no non-Asian strains. Conversely, PCR using Western cagA primers resulted in amplicons in 100% of non-Asian strains, and only one from East Asia. cagA genotyping is useful for molecular epidemiological studies as strains can be completely separated by differences in the cagA 3' region.

Adult↗
PubMed2000

Human scavenger receptor B1 is involved in recognition of apoptotic thymocytes by thymic nurse cells.

Recognition and uptake of apoptotic cells by neighboring phagocytes is essential for the clearance of dying cells without accompanying inflammation or tissue damage. In the thymus, many apoptotic cells are generated in the process of negative selection, and both thymic macrophages (professional phagocytes) and nursing thymic epithelial cells (nursing TEC; nonprofessional phagocytes) recognize and ingest them. However the receptors responsible for this recognition and uptake have not been identified. In the present study, we have established a human nursing TEC line and examined the expression of several genes of the scavenger receptor family considered to be potential receptors for apoptotic cells. Human scavenger receptor-B1 (hSR-B1)/CLA-1, previously shown to recognize apoptotic cells, was strongly expressed in nursing TEC, whereas there was little or no expression of the other scavenger receptors tested: scavenger receptor class A, CD36, or CD68. Suppression of hSR-B1/CLA-1 expression using antisense oligonucleotides decreased the binding of apoptotic thymocytes to nursing TEC by more than 40%. These results indicate that hSR-B1/CLA-1 may play a major role in the clearance of apoptotic cells in the thymus, mediating the recognition and ingestion of apoptotic thymocytes by nursing TEC.

Animals↗
PubMed2000

Relative power contributions of unit discharges simultaneously recorded in the mesencephalic reticular formation.

In order to investigate mutual interactions between neuronal discharges in the mesencepahlic reticular formation, relative power contributions (RPC) were estimated during sleep-wake cycles and serotonin (5HT)-depleted conditions by the administration of parachlorophenylalanine (PCPA). The RPC for most of the neurons dominated in the lower frequency range below 0.4 Hz during rapid eye movement (REM) sleep and the PCPA-treated conditions, which were qualitatively reproduced by the neural network model under global disinhibition. The results supported the hypothesis that the peculiar dynamics of neuronal activities during REM sleep, 1/f fluctuations, were generated by neuronal interactions augmented by the release from the global inhibition of 5HT.

Animals↗
PubMed2000

Semiquantitative immunoblot analysis of nm23-H1 and -H2 isoforms in adenocarcinomas of the lung: prognostic significance.

Total amounts of nm23 protein and relative levels of H1 and H2 isoforms were studied in 27 fresh-frozen samples of pulmonary adenocarcinoma and adjacent non-neoplastic tissues that were obtained at surgery. Semiquantitative immunoblotting with a monoclonal antibody (Pan-242) against nm23 protein demonstrated both isoforms, recognized as 20.5 kDa for H1 and 18.5 kDa for H2, to be present in all cases. Both H1 and H2 levels in neoplastic tissues were higher than in the corresponding non-neoplastic samples. Expression of H2 was usually greater than of H1. The H2/H1 ratio varied from 1.9 to 14.1 (mean value 5.2) in non-neoplastic tissues and 1.0-5.9 (mean value 2.5) in neoplastic tissues, although this ratio did not correlate with any prognostic factor like tumor size, nodal status or distant metastasis (TNM tumor stage). H1 and H2 levels were significantly lower (mean values 4.3 and 2.4) in well-differentiated than in moderately and poorly differentiated adenocarcinomas (8.3 and 3.0) (P < 0.03 and P < 0.05, respectively). These data indicate that H1 and H2 isoform levels correlate with histological differentiation, but not the metastatic potential or stage of pulmonary adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria.

UNLABELLED: Identification of five novel SLC3A1 (rBAT) gene mutations in Japanese cystinuria. BACKGROUND: Cystinuria is an inheritable amino aciduria and has been classified into three subtypes: I, II, and III. One of the genes responsible for cystinuria has recently been identified as SLC3A1 or rBAT, but only type I cystinuria seems to be caused by genetic alterations in rBAT. To our knowledge, thus far 38 mutations in rBAT gene have been described. In this study, we investigated rBAT mutations in Japanese patients and compared the results with the previously reported mutations in other races. METHODS: We investigated 36 Japanese cystinuria patients by mutational analysis of rBAT gene. To identify newly mutated alleles, genomic DNA was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). When an abnormal migration was observed on SSCP, a nucleotide sequence determination was performed. RESULTS: Five novel mutations were identified in five patients, three with missense mutations (L346P, I445T, C673R), one with a 1 bp deletion (1820delT), and one with a 2 bp insertion (1898insTA), and we detected three previously reported polymorphisms. Three of the mutations were homozygous, in whom parents had intermarried, and two were heterozygous for each mutations. Analysis of rBAT in family of the 1898insTA patient revealed that the patient had inherited the mutated allele from his parents. CONCLUSION: Five novel mutations in the rBAT gene have been identified in Japanese patients with cystinuria. A racial difference was not apparent in the position and frequency of the mutations.

Amino Acid Transport Systems, Basic↗