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Biomedical subjects

K Tani

Publications and source records attributed to K Tani.

At least 109 records · Page 6Linked to original sources

Specific lipid-protein interactions in a novel honeycomb lattice structure of bacteriorhodopsin.

In the purple membrane of Halobacterium salinarium, bacteriorhodopsin trimers are arranged in a hexagonal lattice. When purple membrane sheets are incubated at high temperature with neutral detergent, membrane vesicularization takes place, yielding inside-out vesicles with a diameter of 50 nm. The vesicular structure becomes unstable at low temperature, where successive fusion of the vesicles yields a crystal which is composed of stacked planar membranes. X-ray crystallographic analysis reveals that the bacteriorhodopsin trimers are arranged in a honeycomb lattice in each membrane layer and that neighbouring membranes orient in opposite directions. The native structure of the trimeric unit is preserved in the honeycomb lattice, irrespective of alterations in the in-plane orientation of the trimer. One phospholipid tightly bound to a crevice between monomers in the trimeric unit is suggested to act as a glue in the formation of the trimer.

Bacteriorhodopsins↗

[Studies on detection methods for Legionella species from environmental water].

We investigated selective cultivation media and previous treatments of samples suitable for detection of Legionella species from environmental water and for elimination of co-existing microbes which gave rise to an interference with the evaluation of Legionella sp. growth. Twenty thousand U of polymyxin B (PL-B)/ml and 100 micrograms of oxytetracycline (OTC)/ml seem to be useful as additives to MWY selective agar medium. Both antibiotics markedly inhibited the growth of co-existing microbes with almost no influence on the growth of Legionella sp. In the studies on the resistance of 8 strains of Legionella sp., 24 strains of co-existing microbes and 2 standard strains of Staphylococcus aureus and Escherichia coli to acid treatment (0.2 M HCl-KCl, pH 2.2, 25 degrees C, 4 minutes) and heating (50 degrees C, 20 minutes), acid treatment or heating alone showed no inhibition on the growth of almost all strains examined. However, combination with acid treatment after heating resulted in an apparent extinction of almost all microbes except for Legionella sp., Seven strains from co-existing microbes showed an apparent growth inhibition against 8 strains of Legionella sp. with different serotypes and were all identified as Pseudomonas aeurginosa, which were all eliminated by means of the combination with acid treatment after heating. From these results, it was concluded that the combined pre-treatment of water samples with acid after heating and the addition of PL-B and OTC into the selective cultivation medium is an useful method for detection of Legionella sp. from environmental water.

Anti-Bacterial Agents↗

Factors governing the activity in vivo of ribozymes transcribed by RNA polymerase III.

In order to determine the parameters that govern the activity of a ribozyme in vivo, we made a systematic analysis of chimeric tRNAVal ribozymes by measuring their cleavage activities in vitro as well as the steady-state levels of transcripts, the half-lives of transcribed tRNAVal ribozymes, and their activities in both HeLa and H9 cells. These analyses were conducted by the use of transient expression systems in HeLa cells and stable transformants that express ribozymes. Localization of transcripts appeared to be determined by the higher-order structure of each transcribed tRNAVal ribozyme. Since colocalization of the ribozyme with its target RNA is important for strong activity of the ribozyme in vivo, the best system for tRNA-based expression seems to be one in which the structure of the transcript is different from that of the natural tRNA precursor so that processing of the tRNAVal ribozyme can be avoided. At the same time, the structure of the transcript must be similar enough to allow recognition, probably by an export receptor, so that the transcript can be exported to the cytoplasm to ensure colocalization with its target. In the case of several tRNAVal ribozymes that we constructed, inspection of computer-predicted secondary structures enabled us to control the export of transcripts. We found that only a ribozyme that was transcribed at a high level and that had a sufficiently long half-life, within cells, had significant activity when used to withstand a challenge by human immunodeficiency virus type 1.

Animals↗

Alkaline phosphatase, defensin gene expression and effect of myeloid cell growth factors in normal and leukemic cells.

In neutrophils, four different granules are defined, i.e. azurophil, specific, gelatinase and secretary vesicles. In these granules many neutrophil-specific constituents are identified. Some of these constituents have already been cloned and their gene expressions studied. In such constituents, alkaline phosphatase (ALP) and defensin are well known, although their functions are not yet fully clarified. ALP is present in secretary vesicles and has important roles in the diagnosis of some myeloid disorders. On the other hand, defensin is the most abundant functional peptide of neutrophils and is present in azurophillic granules. Which are subdivided into defensin-rich and defensin-poor granules. This review describes the expression of ALP and the defensin gene in normal and leukemic cells and the effect on these genes of myeloid growth factors, such as granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interleukin 3.

Alkaline Phosphatase↗

Myeloperoxidase gene expression and regulation by myeloid cell growth factors in normal and leukemic cells.

Myeloperoxidase (MPO) is present in azurophilic granules which appear in the promyelocyte stage of differentiation, and is the most common functional protein of myeloid cells. With progress in molecular biology, the expression and regulation of MPO have been clarified in normal myeloid and leukemic cells, not only by enzymatical activity but at the gene level MPO expression is affected by the differentiation of myeloid cells, and has been suggested to be regulated by myeloid cell growth factors, such as granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor and interleukin-3. In the past decade the signal transduction from their receptors has been clarified. This review describes the expression and regulation of the MPO gene in myeloid cells including myeloid disorders, such as myeloid leukemia or myelodysplastic syndromes, The effects on MPO by myeloid growth factors and signal transduction from their receptors are also presented.

Bone Marrow Cells↗

CD4/CD8 double-positive adult T cell leukemia with preceding cytomegaloviral gastroenterocolitis.

We present a rare case of adult T cell leukemia (ATL) in which leukemic T cells simultaneously expressed CD4 and CD8 surface antigens and refractory cytomegalovirus (CMV)-induced gastroenterocolitis preceded its clinical onset. A 40-year-old male was admitted to our hospital with abdominal pain and bloody stool. Biopsy specimens of the gastric and rectal mucosa indicated CMV-induced gastroenterocolitis. The patient also proved to be seropositive for human T lymphotropic virus type I (HTLV-I). While being administered gancyclovir for CMV infection, he presented hepatomegaly and systemic lymphadenopathy. Monoclonal expansion of lymphoid cells integrated with HTLV-I genome was observed. He underwent a LSG15 regimen and hepatomegaly and lymphadenopathy improved markedly. Gastroenterocolitis also improved, but the symptoms did not disappear completely. CMV-induced diseases are prevalent among immunosuppressed patients. Although there was no evidence that this patient had ATL on admission, it is likely that he was severely immunodeficient. CMV can easily infect damaged mucosa. ATL cells often infiltrate gastrointestinal mucosa and may have triggered CMV gastroenterocolitis in this case.

Adult↗

[Investigation of plasma levels of etodolac and urine PGE2 in patients with rheumatoid arthritis].

13 women patients (containing high-aged, mean age 71.9 years) with rheumatoid arthritis (RA) (10 with normal renal function and 3 with moderate renal insufficiency) participated in a 5-day study to assess the effects of etodolac on renal function and the necessity of dose adjustment. After no drug-free day, etodolac, 200 mg b.i.d. was started. The plasma levels of etodolac were similar in both normal control in phase I studies and throughout this study. Although the mean urine PGE2 concentration in renal insufficient group was significantly lower than that of normal renal function group, the mean urine PGE2 concentration in after etodolac administration was not different from that in before its administration in each group. This result suggested that renal adverse reactions with etodolac were low in incident. Moreover, it was required to consider that glucocorticoid might influence renal and/or hepatic excretion of etodolac. In this study the glucocorticoid was tend to be administrated in the patients with moderate renal insufficiency. Those glucocorticoid group showed lower levels of etodolac in blood serum (monitored by AUC0-8, day 4 Cmin and day 5 Cmin) than non-glucocorticoid group did, but not significantly. Interestingly, there is a negative correlation (r = -0.442) between AUC0-8 at day 1 and urine PGE2 at day 5 in glucocorticoid group. The levels of etodolac in blood serum in normal renal function group were also not significant in difference from that in the moderate renal insufficient group. These results suggest that the dose adjustment of etodolac in high-aged RA patients with moderate renal insufficiency can be excluded.

Aged↗

ADP-ribosylation factor-1 is sensitive to N-ethylmaleimide.

The treatment of normal rat kidney cells with N-ethylmaleimide caused the release of beta-COP, a component of coatomer, from the Golgi apparatus without causing disassembly of the organelle. The release of beta-COP, which was not due to depolymerization of microtubules, was markedly blocked by the activation of GTP-binding proteins by aluminum fluoride or a nonhydrolyzable analogue of GTP. To determine which component is N-ethylmaleimide-sensitive, we reconstituted the recruitment of coatomer from the bovine brain cytosol onto the Golgi apparatus in digitonin-permeabilized cells. In cells treated with N-ethylmaleimide before permeabilization, beta-COP was still recruited onto the Golgi apparatus. In contrast, beta-COP was not recruited when N-ethylmaleimide-treated bovine brain cytosol was used. These results suggest that the N-ethylmaleimide-sensitive factor(s) are present in the cytosol. It is known that coatomer and ADP-ribosylation factor-1 (ARF1) are the only cytoplasmic proteins needed for the assembly of Golgi-derived coated vesicles. N-Ethylmaleimide treatment of a coatomer-rich fraction did not affect the binding of beta-COP to the Golgi apparatus, whereas the same treatment of an ARF-rich fraction abolished beta-COP binding. Similar results were obtained using purified recombinant ARF1. Concomitant with inactivation, 0.85 mol of N-ethylmaleimide was incorporated into 1 mol of ARF1. ARF1 contains only one cysteine residue (Cys-159), which is located near the base moiety of the bound guanine nucleotide.

ADP-Ribosylation Factor 1↗

Functional polymorphism of -141C Ins/Del in the dopamine D2 receptor gene promoter and schizophrenia.

Several studies showed the density of D2 receptors was elevated in postmortem brains from schizophrenics. Genes which operate at the level of gene activation may be associated with the pathogenesis of schizophrenia. Arinami et al. [(1997) Human Molecular Genetics 6, 577-582] found a polymorphism in the 5'-flanking region of the D2 receptor gene designated as -141C Ins/Del. The promoter activity by luciferase assay of a plasmid containing the -141C Ins allele was higher than in the one containing the -141C Del allele. In addition, the -141C Ins allele frequency was significantly higher in schizophrenics than in control subjects. We replicated the -141C Ins/Del polymorphism in 170 schizophrenics and 121 healthy control subjects. The number of schizophrenics with the -141C Ins/Ins genotype was significantly higher than that of control subjects (P = 0.038). The frequency of the -141C Ins allele was significantly increased in the schizophrenics compared with the control subjects (P = 0.042). The mean age of onset for the patients with -141C Ins/Del was significantly lower than that for the patients with -141C Ins/Ins (P = 0.029). There was no association between the genotype and either positive symptoms or the response to antipsychotic medication. Our results suggest that the -141C Ins/Del polymorphism may affect the susceptibility to schizophrenia.

Adult↗

AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene.

The AML1 and PEBP2beta/CBFbeta genes encode the DNA-binding and non-binding subunits, respectively, of the heterodimeric transcription factor, PEBP2/CBF. Targeting each gene results in an almost identical phenotype, namely the complete lack of definitive hematopoiesis in the fetal liver on embryonic day 11.5 (E11.5). We examined and compared the expression levels of various hematopoiesis-related genes in wild type embryos and in embryos mutated for AML1 or PEBP2beta/CBFbeta. The RNAs were prepared from the yolk sacs of E9.5 embryos, from the aorta-gonad- mesonephros regions of E11.5 embryos and from the livers of E11.5 embryos and RT-PCR was performed to detect various gene transcripts. Transcripts were detected for most of the hematopoiesis-related genes that encode transcription factors, cytokines and cytokine receptors, even in tissues from homozygously targeted embryos. On the other hand, PU.1 transcripts were never detected in any tissue of AML1(-/-) or PEBP2beta/CBFbeta(-/-) embryos. In addition, transcripts for the Vav, flk-2/flt-3, M-CSF receptor, G-CSF receptor and c-Myb genes were not detected in certain tissues of the (-/-) embryos. The results suggest that the expression of a particular set of hematopoiesis-related genes is closely correlated with the PEBP2/CBF function.

Animals↗

Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders.

BACKGROUND: Heils et al found a functional polymorphism in the transcriptional control region upstream of the serotonin transporter gene at the SLC6A4 locus. The transcriptional promoter activity of the short (s) form was less than twice that of the long (l) form of the serotonin transporter promoter gene. In addition, they found individuals with the s form with associated neurotic characteristics (e.g., anxiety, anger, hostility, and depression). The purpose of this study was to determine whether or not there is an association between this functional polymorphism and mood disorders. METHODS: The l/s polymorphism was studied in 80 patients with mood disorders and 92 control subjects. RESULTS: There was statistically no difference between mood disorders and healthy controls in either the genotype or the allele frequency. There was statistically no difference between the genotype and subdiagnosis, family history, single/recurrent episodes of depressive disorders, suicide attempts, or the mean age of onset. CONCLUSIONS: Our results suggest there is no association between the l/s polymorphism of the serotonin transporter gene and mood disorders.

Adult↗

NSF is required for the brefeldin A-promoted disassembly of the Golgi apparatus.

N-Ethylmaleimide-sensitive factor (NSF) is required for multiple pathways of vesicle-mediated protein transport. Microinjection of a monoclonal anti-NSF antibody almost completely blocked brefeldin A-promoted Golgi disassembly without affecting the rapid release of beta-COP, a subunit of the Golgi coat proteins (COPI), from the Golgi apparatus. Similar results were obtained using a dominant-negative NSF which is known to compete with endogenous NSF. The present results suggest that an NSF-mediated step is present in the brefeldin A-promoted disassembly of the Golgi apparatus.

Animals↗

Synthesis and pharmacological activities of 13-dehydro derivatives of primary prostaglandins.

13-Dehydro derivatives of prostaglandin E1, E2, E3, F1 alpha and F2 alpha were synthesized. Compared with natural prostaglandins, 13-dehydro analogues were found to exhibit more potent inhibitory activity against human platelet aggregation and relaxation of guinea-pig isolated trachea, while they showed less potent activity of contraction of guinea-pig isolated ileum.

Animals↗

Polymorphism in the promoter region of the alpha 2A adrenergic receptor gene and mood disorders.

Alpha 2 adrenergic receptors are thought to play a crucial role in the etiology or treatment of mood disorders. Polymorphism(s) in the promoter region of the alpha 2 receptor may affect the gene expression and be associated with mood disorders. We studied the previously reported polymorphisms of the alpha 2A receptor gene at position-1291 in 114 healthy controls and 103 mood disorder patients. There was statistically no difference between controls and patients in either the genotype or the allele frequency. There was statistically no difference between the genotype and the clinical characteristics. Our results suggest there is no association between this polymorphism in the promoter region of the alpha 2A receptor gene and mood disorders.

Alleles↗

XAFS spectra from reflectivity measurements.

The reflectivity of TiSi(2) films was measured as a function of photon energy E at the Ti K-edge region at a glancing angle theta close to the critical angle theta(C) of total reflection. TiSi(2) silicide films (about 30 nm thickness) were prepared by silicidation of Ti thin films deposited on Si(001) substrates. Since the Fresnel reflectivity R(theta,E) is a function of the dispersion delta(E) and of the absorption beta(E), the absorption beta(E) which carries the XAFS signal can be solved as beta(theta,delta,R) for observed reflectivity R and for estimated delta. The dispersion delta(E) is related to the absorption beta(E) by the Kramers-Kronig (K-K) relations since the refractive index is n(E) = 1 - delta(E) - ibeta(E). beta(E) was calculated from the observed reflectivity R(theta,E) using theoretical values for initial delta(E). Titanium K-edge XAFS for TiSi(2) was extracted from the reflectivity by 'ReflXAFS'.

Journal Article↗

X-ray absorption fine structure of V(2)O(5) and Li(x)V(2)O(5).

Vanadium K-edge XAFS measurements of five compounds were carried out. The compounds studied were crystalline V(2)O(5) and four types of Li(x)V(2)O(5) with different insertion levels x, which show different EMFs (2.0-3.4 V). The EXAFS data analysis shows no remarkable difference in the V-O distances in the five compounds, showing that the structure of the VO(5) square pyramids changes only slightly as lithium atoms are intercalated into the V(2)O(5). In the XANES spectra, three peaks are observed for crystalline V(2)O(5) and Li(x)V(2)O(5) (3.4 V). When the EMF is decreased, the intensity difference between the first and second peaks disappears and the third peak shifts to lower energy. The XANES data were analysed using full multiple-scattering calculations. In the calculated spectra the intensity of the first peak increases as the V(2)O(5) intercalates lithium atoms.

Journal Article↗

Interferon-alpha-induced G1 phase arrest through up-regulated expression of CDK inhibitors, p19Ink4D and p21Cip1 in mouse macrophages.

The mechanism of cell cycle arrest induced by interferon-alpha (IFN-alpha) was analysed using a mouse macrophage cell line, BAC1.2F5A. IFN-alpha added in media before mid-G1 prohibited cells from entering S phase. The blockage of G1/S transition was associated with diminuition of both cyclin D1/cdk4- and cyclin E/cdk2-associated kinase activities. G1 cyclin-associated kinase activities were down-regulated quickly after the addition of IFN-alpha. Cells treated with IFN-alpha contained excess amounts of cdk inhibitors which down-regulated G1 cyclin/cdk-associated kinase activities in the proliferating cells and this action was counteracted by exogenously-supplied recombinant cyclin D2/cdk4 complexes. In parallel, accumulation of p19Ink4D and p21Cip1, and their attachment to cdks were up-regulated quickly after the addition of IFN-alpha. Expression of p19Ink4D and p21Cip1 was potentiated transcriptionally. We concluded that increased attachment of up-regulated cdk inhibitors including p19Ink4D and p21Cip1 to G1 cyclin/cdk complexes contributed to diminuition of G1 cyclin/cdk-associated kinase activities and resulting G1 phase arrest during the early phase of treatment with IFN-alpha.

Amino Acid Sequence↗