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Biomedical subjects

K Yamaguchi

Publications and source records attributed to K Yamaguchi.

At least 379 records · Page 21Linked to original sources

[Penicillin-resistant Streptococcus pneumoniae infections: current trends in epidemiology and antibiotic chemotherapy].

The world-wide emergence of penicillin-resistant Streptococcus pneumoniae has led to dilemmas in the management of pneumococcal infections. Furthermore, most penicillin-resistant pneumococci are simultaneously resistant to a wide variety of other antibiotics, including cephalosporins, macrolides and tetracyclines. Epidemiological surveys in Japan demonstrated that 30-50% of clinical isolates were penicillin-insusceptible(MIC: > or = 0.125 microgram/ml). At present time most penicillin-resistant pneumococcal pneumonia cases are well treated with penicillin or cephalosporin, but significant numbers of treatment failures were reported in meningitis patients. Data from healthy mice model of pneumonia clearly showed that carbapenems and vancomycin are more active than cefotaxime or penicillin in high dose. Careful and continuous surveys for trends in antibiotic resistance and clinical impacts of antibiotic-resistant pneumococci are warranted.

Animals↗

A case of poorly differentiated hilar lung adenocarcinoma of an unidentified histological type.

The patient was a 74-year-old man, a physician, whose chief complaint was an unproductive cough. The shadow of a mass was seen at the hilum of the left lung, and the mediastinal lymph nodes on both sides were swollen. No histological diagnosis was obtained even after bronchoscopy, including transbronchial needle aspiration biopsy, but large-cell carcinoma of the lung was diagnosed on the basis of ultrasound-guided biopsy of a shadow in the liver suspected of being a metastatic tumor (T2N3M1, Stage IV). Two courses of chemotherapy (CBCDA + VDS) failed to gain any improvement, and the pain resulting from recurrent bone metastases was managed mainly by the administration of the best supportive care. The patient was readmitted to the hospital after development of numbness in the right upper extremity followed by complication of pneumonia and heart failure, and he passed away. Autopsy revealed a primary hilar lung tumor with a histological diagnosis of poorly differentiated adenocarcinoma.

Adenocarcinoma↗

[Clinical experiences of endotoxin removal columns in septic shock due to urosepsis: report of three cases].

Clinical experiences of endotoxin removal using polymyxin B immobilized fiber column (PMX) in three septic shock patients are reported. The patients were referred to our hospital with complaints of high fever and severe pain during urination. Physical examination and laboratory data revealed severe hypotension, tachycardia, and pyuria. Diagnoses of septic shock due to urosepsis were made. After antibiotic therapy and anti-shock therapy, direct hemoperfusion using polymyxin B immobilized fiber column (PMX) was carried out. Thereafter, cardiovascular instabilities were improved without increasing the supply of catecholamines. PMX therapy for systemic inflammatory response due to infection was effective in treatment of cardiovascular instabilities.

Aged↗

[In vitro and in vivo antibacterial activities of azithromycin].

In Vitro and in vivo antibacterial activities of azithromycin were compared with those of macrolides and other antimicrobial agents. In the in vitro activity azithromycin has a potent activity against both gram-positive and gram-negative bacteria, but against the latter organisms the other macrolides have little potent activity. The in vitro results demonstrate that azithromycin has a high potent activity against respiratory pathogens such as erythromycin-susceptible staphylococci, streptococci (except for organisms possessing erm gene), H, influenzae, B. prtussis, Legionella spp., M. pneumoniae, C. trachomatis. In the pharmacokinetic of azithromycin in mice, it is found that its half life is longer than the other macrolides and the concentration of it in polymorphonuclear leukocytes and lung tissues is higher than the other macrolides. These specific properties in the pharmacodynamic and the in vitro antibacterial activities reflect the therapeutic efficacies in experimental infection models. Finally, the therapeutic efficacies of azithromycin in various infection models better than those of the other macrolides.

Animals↗

Structure and expression of ovine complement receptor type 2.

The structure of sheep complement receptor type 2 (CR2) was characterised by cDNA cloning, protein sequencing and immunoprecipitation. The primary structure of sheep CR2 is similar to known mammalian homologues but the higher-order structure is unusual. Two distinct CR2 isoforms occur, one of which is ubiquitinated in the cytoplasmic domain, and the two molecular forms are expressed at the cell surface as non-covalently associated dimers. The percentage of sheep B-cells that express CR2 changes during development and varies between different body compartments. CR2+ and CR2 B-cell subsets also differ in the expression of other surface markers and in functional properties. Differential expression of CR2 may, therefore, delineate B-cells that arose by alternative developmental pathways, or it could be a marker for B-cells at different phases of antigen exposure.

Animals↗

Hypertrophic stimuli augment expression of cMG1/ERF-1, a putative zinc-finger motif transcription factor, in rat cardiomyocytes.

We isolated the gene for cMG1/ERF-1, a known putative zinc-finger transcription factor, by differential display of mRNA extracted from cardiomyocytes with and without leukemia inhibitory factor (LIF) stimulation. LIF induced cMG1/ERF-1 mRNA at 15 min, and levels peaked at 10-fold initial levels at 30 min. cMG1/ERF-1 expression was inhibited by AG490 (JAK2 inhibitor) and genistein, but was unaffected by PD98059 or wortmannin. Phenylephrine, angiotensin II and endothelin-1 also induced cMG1/ERF-1 expression. Mechanical stretch in vitro and acute pressure overload in vivo increased cMG1/ERF-1 expression. To our knowledge, this is the first report showing that the cMG1/ERF-1 gene can be induced by various hypertrophic stimuli, and that Janus kinase 2 is involved in this process.

Angiotensin II↗

Analysis of anatoxin-a in freshwaters by automated on-line derivatization-liquid chromatography-electrospray mass spectrometry.

Anatoxin-a is a toxin produced from cyanobacterial blooms in freshwaters. In order to determine trace anatoxin-a in freshwaters, an automated on-line derivatization procedure with fluorenyl methylchloroformate using liquid chromatography-electrospray ionization mass spectrometry was developed. Anatoxin-a was extracted using solid-phase extraction with adequate recovery (75.7+/-7.2%, n=6) at 20 ng/l. The limits of quantification and detection were calculated to be 15.2 ng/l and 2.1 ng/l, respectively, using selected ion monitoring.

Bacterial Toxins↗

Structural analysis of the TNIT4 genes encoding nitrilase-like protein from tobacco.

Nitrilase (nitrile aminohydrolase, EC 3.5.5.1) catalyzes the hydrolysis of indole-3-acetonitrile (IAN) to indole-3-acetic acid (IAA). The Arabidopsis thaliana genome has four nitrilase genes (NIT1 to NIT4), while tobacco (Nicotiana tabacum) has only NIT4 homologs (TNIT4A and TNIT4B) and no NIT1 to NIT3 homologs. We have cloned the promoter region of TNIT4B and determined the transcriptional start sites which are the same sites in both TNIT4A and TNIT4B. The TNIT4 genes are expressed in various organs at low levels. The positions of the exon-intron splicing junctions in Arabidopsis NIT1 to NIT3 are completely conserved in TNIT4A.

Aminohydrolases↗

Structure and distribution of rat menin mRNA.

Menin is a protein product of a tumor suppressor gene MEN1, mutations of which are responsible for multiple endocrine neoplasia type 1, an autosomal dominant familial cancer syndrome. We isolated rat menin cDNA clones from a fetal rat brain cDNA library. We also determined the nucleotide sequence of the protein coding region of mouse menin cDNA, which was partly registered in the expressed sequence tag (EST) database. Deduced amino acid sequences of rat and mouse menin are highly homologous to human menin. All of the previously reported disease-associated missense mutations and single amino acid deletions were observed at the residues that are conserved among these three species. Rat MEN1 transcripts were detected not only in the endocrine tissues but also in the tissues of the nervous, digestive, reproductive and immune systems. The MEN1 transcripts were abundantly expressed in the developing rat brain on day 14-18 of gestation. Immunoblotting and immunocytochemical analysis of the COS-7 cells transfected with a rat menin-expression vector revealed that the translated product has a molecular mass of approximately 70 kDa, and is localized mainly in the nucleus. These findings are consistent with those reported on human menin.

Amino Acid Sequence↗

Molecular cloning of EDG-3 and N-Shc genes from the puffer fish, Fugu rubripes, and conservation of synteny with the human genome.

EDG-3 is a receptor for sphingosine-1-phosphate mapped on human chromosome 9q22.1-q22.2. We used the compact Fugu genome for its linkage analysis. The Fugu EDG-3 was composed of one intron and two exons, encoding a 384 amino acid protein that has 56.9% homology with the human EDG-3. Approximately 3 kb apart, a neuronal Shc (N-Shc) gene was identified. It spans 7 kb containing 12 coding exons, and has an overall 53.4% similarity with the human protein. We mapped the human N-Shc gene to chromosome 9q21.3-q22.2. This is the first report of the genomic structure and the linkage of these two genes conserved between Fugu and human.

Amino Acid Sequence↗

Cellular source(s) of platelet-activating-factor acetylhydrolase activity in plasma.

Platelet activating factor (PAF) is immediately degraded and inactivated in the bloodstream by plasma PAF acetylhydrolase (PAF-AH). Although plasma PAF-AH-like activity was secreted in vitro from various cell types such as macrophages and hepatocytes, the exact cellular source(s) of this enzyme activity in vivo remains unclear. There is a naturally-occurring missense mutation (V279F) in the plasma PAF-AH gene in the Japanese population which results in complete loss of the enzyme activity. We analyzed 52 Japanese who had received an allogeneic bone marrow transplant and maintained donor-derived hematopoiesis. Ten recipients had chimeric plasma PAF-AH genotypes between the donor-derived peripheral blood leukocytes and the recipient-derived epithelial cells of buccal mucosa. Multiple regression analysis demonstrated that PAF-AH activity in plasma depended on the donor's genotype (standardized regression coefficient = 0.68, P < 0.0001), but not on the recipient's genotype (p = 0.48). One recipient who was a V279F homozygote in leukocytes and wild type homozygote in buccal mucosa had undetectable PAF-AH activity in plasma. We conclude that most of the PAF-AH activity in human plasma originates from hematopoietic lineage cells.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.

Based on the relative expression of CD11c and CD1a, we have identified three fractions of dendritic cells (DCs) in human peripheral blood, including a direct precursor of Langerhans cells (LCs). The first two fractions were CD11c+ DCs, comprised of a major CD1a+/CD11c+ population (fraction 1), and a minor CD1a-/CD11c+ component (fraction 2). Both CD11c+ fractions displayed a monocyte-like morphology, endocytosed FITC-dextran, expressed CD45RO and myeloid markers such as CD13 and CD33, and possessed the receptor for GM-CSF. The third fraction was comprised of CD1a-/CD11c- DCs (fraction 3) and resembled plasmacytoid T cells. These did not uptake FITC-dextran, were negative for myeloid markers (CD13/CD33), and expressed CD45RA and a high level of IL-3Ralpha, but not GM-CSF receptors. After culture with IL-3, fraction 3 acquired the characteristics of mature DCs; however, the expression of CD62L (lymph node-homing molecules) remained unchanged, indicating that fraction 3 can be a precursor pool for previously described plasmacytoid T cells in lymphoid organs. Strikingly, the CD1a+/CD11c+ DCs (fraction 1) quickly acquired LC characteristics when cultured in the presence of GM-CSF + IL-4 + TGF-beta1. Thus, E-cadherin, Langerin, and Lag Ag were expressed within 1 day of culture, and typical Birbeck granules were observed. In contrast, neither CD1a-/CD11c+ (fraction 2) nor CD1a-/CD11c- (fraction 3) cells had the capacity to differentiate into LCs. Furthermore, CD14+ monocytes only expressed E-cadherin, but lacked the other LC markers after culture in these cytokines. Therefore, CD1a+/CD11c+ DCs are the direct precursors of LCs in peripheral blood.

Antigens, CD1↗

A novel splicing mutation (894-9 G --> A) of the MEN1 gene responsible for multiple endocrine neoplasia type 1.

Germline MEN1 gene mutations are responsible for multiple endocrine neoplasia type 1 (MEN1), a dominantly inherited cancer syndrome. We identified a MEN1 germline mutation 894-9 G --> A in three MEN1 patients from two unrelated families. This mutation was not present in any of the 100 blood samples from normal volunteers. The wild type MEN1 sequence was lost in the patient's pancreatic tumor. Abnormal mRNA was identified in the tumor, which retained an intronic sequence indicating aberrant mRNA splicing at a newly created splicing acceptor site. These findings indicate that this nucleotide substitution is, though previously reported to be a polymorphism, a causative splicing mutation.

Adult↗

Rapid quantification of HTLV-I provirus load: detection of monoclonal proliferation of HTLV-I-infected cells among blood donors.

In this report, we quantified HTLV-I provirus load using the AmpliSensor system, which utilizes fluorescence to measure PCR products. With this method, provirus loads could be measured within 6 hr, and the results obtained correlated well with those obtained by other methods. Samples from 256 blood donors, who were positive for antibodies against HTLV-I, were analyzed, showing that provirus load ranged from less than 0.1% to 56% among carriers. We analyzed the association between provirus load and the biomarkers age and sex and found that it was not influenced by either. Provirus load was better correlated with soluble interleukin-2 receptor (sIL-2R) levels than with antibody titer against the virus. Among 18 blood donors with high provirus load (more than 10%), Southern blotting detected monoclonal integration of HTLV-I in infected cells in 2 cases, both of them showing high sIL-2R levels (more than 900 U/ml). Sequential analyses of provirus load showed stable levels of provirus in the same carriers, suggesting that some factors other than age or sex determined provirus load in infected individuals. Thus, this rapid method is a useful tool for the early detection of adult T-cell leukemia and other HTLV-I-associated diseases.

Adolescent↗

Staurosporine enhances cAMP-induced expression of neural-specific gene VGF and tyrosine hydroxylase.

Cyclic AMP transiently stimulates transcription of specific genes in the nervous system, including neural-specific gene VGF. The simultaneous presence of staurosporine (SSP) caused a progressive, rather than transient, increase in VGF mRNA levels during the cAMP-induced differentiation of human neuroblastoma cells. This steady increase does not appear to be due to increased stability of VGF mRNA. This synergy between cAMP and SSP was also observed at the protein level for tyrosine hydroxylase. These findings suggest the presence of cellular machinery that counteracts the decline of cAMP-induced gene expression.

Animals↗

Identification of a novel gene, LDOC1, down-regulated in cancer cell lines.

By screening for differentially expressed genes in cancer cells, using the RNA differential display (DD) technique, we identified a novel cDNA, LDOC1, that is down-regulated in some cancer cell lines. A Northern blot analysis revealed no expression in pancreatic and gastric cancer cell lines but ubiquitous expression in normal human tissues. This new gene was mapped on chromosome Xq27 and the predicted protein sequence showed no similarity to known sequences in the database except for a leucine zipper-like motif at the N-terminal region and a proline-rich region that shares marked similarity to an SH3-binding domain. In an enhanced green fluorescent protein (EGFP) assay, the EGFP-LDOC1 fusion protein was localized in the nucleus. Although the function of LDOC1 is still unknown, our results suggest that this novel gene codes for a nuclear protein, and down-regulation of LDOC1 may have an important role in the development and/or progression of some cancers.

Amino Acid Sequence↗