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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 397 records · Page 22Linked to original sources
PubMed1995

Cytokine signaling through nonreceptor protein tyrosine kinases.

Cytokines are a family of soluble mediators of cell-to-cell communication that includes interleukins, interferons, and colony-stimulating factors. The characteristic features of cytokines lie in their functional redundancy and pleiotropy. Most of the cytokine receptors that constitute distinct superfamilies do not possess intrinsic protein tyrosine kinase (PTK) domains, yet receptor stimulation usually invokes rapid tyrosine phosphorylation of intracellular proteins, including the receptors themselves. It is now clear that these receptors are capable of recruiting or activating (or both) a variety of nonreceptor PTKs to induce downstream signaling pathways. Thus, the intracytoplasmic structure of cytokine receptors has evolved so as to allow the combined action of different PTK family members expressed in different cell types, which may ultimately determine the activity of cytokines.

Animals↗
PubMed1995

Epigenetic changes encompassing the IGF2/H19 locus associated with relaxation of IGF2 imprinting and silencing of H19 in Wilms tumor.

In most tissues IGF2 is expressed from the paternal allele while H19 is expressed from the maternal allele. We have previously shown that in some Wilms tumors the maternal IGF2 imprint is relaxed such that the gene is expressed biallelically. We have now investigated this subset of tumors further and found that biallelic expression of IGF2 was associated with undetectable or very low levels of H19 expression. The relaxation of IGF2 imprinting in Wilms tumors also involved a concomitant reversal in the patterns of DNA methylation of the maternally inherited IGF2 and H19 alleles. Furthermore, the only specific methylation changes that occurred in tumors with relaxation of IGF2 imprinting were solely restricted to the maternal IGF2 and H19 alleles. These data suggest that there has been an acquisition of a paternal epigenotype in these tumors as the result of a pathologic disruption in the normal imprinting of the IGF2 and H19 genes.

Alleles↗
PubMed1995

Secondary structure and folding topology of the DNA binding domain of interferon regulatory factor 2, as revealed by NMR spectroscopy.

The secondary structure elements of the DNA-binding domain of mouse interferon regulatory factor 2 [IRF-2(113)] were determined by heteronuclear multidimensional NMR spectroscopy. The sequential NOE connectivities, amide proton exchange rates, and 3JHN alpha coupling constants indicated the presence of three alpha-helical regions and four short beta-strands connected through relatively long loops. The long range NOEs indicated the four strands form an antiparallel beta-sheet and the three alpha-helices form a bundle on the sheet. The arrangement of the secondary structure elements and the overall folding topology resemble those of the DNA binding domains of bacterial activator CAP, heat shock transcription factors, and fork-head proteins, although there is no sequence homology among them.

Amino Acid Sequence↗
PubMed1995

Possible involvement of the transcription factor ISGF3 gamma in virus-induced expression of the IFN-beta gene.

Two virus-inducible transcription factors, IRF-1 and IRF-2 have been identified as an activator and a repressor, respectively, of the type I interferon (IFN) genes. Recent studies with mice carrying null mutations for the IRF-1 or IRF-2 alleles have revealed the existence of IRF-1-dependent and -independent pathways mediating IFN-beta gene induction. Here we report that the expression of an IRF family member ISGF3 gamma is induced upon viral infection in IRF-1-/-, IRF-2-/- embryonic fibroblasts. Furthermore, ISGF3 gamma can bind to a virus-inducible promoter element in the IFN-beta gene. These results suggest that ISGF3 gamma or complex containing ISGF3 gamma is involved in the IRF-1-independent pathway mediating IFN-beta gene regulation.

Amino Acid Sequence↗
PubMed1995

Cholecystokinin-B/gastrin receptor: a novel molecular probe for human small cell lung cancer.

The brain-gut hormones, gastrin and cholecystokinin, have a trophic effect on the gastrointestinal mucosa in vivo and promote the growth of several neoplastic cell lines. In this study, cholecystokinin-B/gastrin receptor has been demonstrated to provide a novel molecular marker for the diagnosis of small cell lung cancer by using biopsy specimens. Physiological expression of the receptor mRNA is detectable in particular areas of the human brain, stomach, and pancreas but not in the lung. The receptor mRNA was detected selectively in all small cell lung cancer (10 cases) with a RT-PCR assay. By contrast, it was detectable in only 1 of 13 squamous cell carcinomas or 21 adenocarcinomas of the lung. Thus, the cholecystokinin-B/gastrin receptor could be an attractive therapeutic target for small cell lung cancer.

Adenocarcinoma↗
PubMed1995

The association among fat distribution, physical fitness, and the risk factors of cardiovascular disease in obese women.

The purpose of this study was to see whether fat distribution and physical fitness are independent risk factors of cardiovascular diseases in obese women. Seventy-four obese women aged 19 to 65 years participated in this study. The data were collected on plasma lipid profiles, plasma glucose and insulin during an oral glucose tolerance test, blood pressure, fat distribution determined by the waist to hip ratio (WHR), total body fat determined by the hydrostatic weighing method and a direct measurement of blood lactate threshold. Significant correlations were found between WHR and plasma cholesterol (TC), plasma LDL cholesterol (LDL-c) and LDL-c to the plasma HDL cholesterol ratio (LDL-c/HDL-c), independent of age, percent body fat, and VO2 per lean body mass at blood lactate threshold (LT). On the other hand, LT was significantly related to the area under the curve of insulin during OGTT (insulin area) and DBP, independent of age, percent body fat, and WHR. In conclusion, both fat distribution and physical fitness are considered to be independently related to some important risk factors in obese women after adjustment for percent body fat.

Adipose Tissue↗
PubMed1995

Changes in lymphocyte beta 2-adrenoceptors after hepatic resection.

Hepatic resection promotes such a high degree of surgical stress that it induces deterioration of various vital functions, which may involve the breakdown of signal transduction systems. To investigate the influence of surgical stress on signal transduction, we studied ligand-receptor specific binding activity after hepatic resection, focusing on lymphocyte beta 2-adrenoceptors. The maximum binding capacity (Bmax) and the dissociation constant (KD) were determined by radioligand binding assay using (-)3H-CGP12177 as a ligand. In the hepatectomy group, Bmax significantly decreased from 1380 +/- 109 to 799 +/- 49 receptors/cell on postoperative day (POD) 3 and to 802 +/- 93 receptors/cell on POD 7 (P < 0.05). In the control group, however, it did not significantly change after the operation. No significant changes in KD were found in either of these groups. The Bmax alteration was not due to the redistribution of lymphocyte subsets or receptor down regulation, but to the decrease in the Bmax of the individual subset. The hepatectomy group was divided into two groups according to the postoperative arterial ketone body ratio (AKBR): Group A, AKBR maintained at 0.7 or more; and Group B, AKBR decreased to below 0.7. The Bmax decrease, a percentage of the preoperative value, of Group B was significantly smaller than that of Group A (48.4 +/- 3.9 and 72.3 +/- 7.3%, respectively, P < 0.05). These results suggest that intense surgical stress, produced by hepatic resection, may influence even ligand-receptor binding parameters, and the decrease in AKBR can indicate the magnitude of surgical stress.

Adrenergic beta-Antagonists↗
PubMed1995

Regulation of the interferon system and cell growth by the IRF transcription factors.

Induction of gene transcription in response to extracellular stimuli constitutes an essential aspect of host defense mechanisms. Interferons (IFN) are families of cytokines that have been discovered and extensively characterized in the context of host defense against viral infections. In elucidating the mechanism of transcriptional induction of the IFN genes by viruses, we have discovered two structurally related transcription factors, Interferon regulatory factor 1 (IRF-1) and IRF-2. These two factors, however, function not only as regulators of the IFN system, but are also key transcription factors in the regulation of cell growth and apoptosis. Thus, these studies uncover a complex gene transcription network in which the fate of cellular responses is determined by how the IRF transcription factors function in conjunction with other factors on the promoters of distinct genes under different conditions of the cells.

3T3 Cells↗
PubMed1995

Use of a new oligonucleotide probe for detection of colonization factor antigen III gene in enterotoxigenic Escherichia coli.

An alkaline phosphatase-labeled 30-mer oligonucleotide probe was designed to detect the gene for pilus colonization factor antigen III (CFA/III) of the human type of enterotoxigenic Escherichia coli (ETEC). The CFA/III probe was used to identify CFA/III-producing ETEC among 303 Escherichia coli obtained from subjects with traveler's diarrhea. Six isolates positive for the CFA/III gene were found. This result was confirmed immunologically by using a specific monoclonal antibody developed against CFA/III. These six isolates, isolated from travelers returning from India, Pakistan and China, were all positive for the gene of heat-labile enterotoxin and possessed an identical serotype (025:H-).

Antigens, Bacterial↗
PubMed1995

A method to estimate the potency of the mu-component of an opioid having mixed mu-, and kappa- and/or delta-agonist activities.

The SC administration of either typical mu-agonists such as morphine, pethidine, fentanyl and levorphanol or a mixed mu- and delta-agonist like [D-Ala2, D-Leu5]-enkephalin to 10-day-old rats produced loss of righting reflex. Additionally, the loss of righting reflex induced by these opioid agonists was antagonized by naloxone, an opioid antagonist having a preference for mu-receptors, but by neither nor-binaltorphimine nor naltrindole, a specific kappa- or delta-antagonist, respectively, indicating that the loss of righting reflex was produced by the interaction of an opioid with mu-receptors. Moreover, the potency of each opioid agonist relative to that of morphine estimated by the present in vivo method was similar to that determined by the traditional in vitro isolated preparation. In contrast to mu-agonists, neither typical kappa-agonists such as U-50, 488H, ketocyclazocine, pentazocine and butorphanol, nor a selective delta-agonist like [D-Pen2, D-Pen5]-enkephalin affected the righting reflex of 10-day-old rats, indicating that mu-agonists, but neither kappa- nor delta-agonists, produced the naloxone-reversible loss of righting reflex in infant rats. By employing the present in vivo method to estimate the mu-agonist activity of an opioid with mixed agonist activities, it was indicated that the mu-agonist activity of ethylketocyclazocine, which had been employed as a representative kappa-agonist, was essentially the same as that of morphine, a representative mu-agonist.

Animals↗
PubMed1995

New design of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) lung imaging in the patient with lung cancer.

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was injected intravenously into primary non small cell lung carcinoma patients (n = 17). The average pixel count ratios of the cancerous area to the whole lung was measured in the initial and delayed images. In the initial image, this ratio was less than 1.0 for the entire group of patients, and was thought to reflect decreased blood flow in the cancerous tissues. The rate of counts within a ROI in the delayed image to counts in the same ROI in the initial image was also calculated and called the remain rate. The remain rate (delayed count/initial count) was significantly higher in the cancerous area than in the whole lung (0.65 +/- 0.30, median 0.62, 0.38 +/- 0.05, median 0.38, p < 0.01). This observation was thought to be due to a relative decrease in the blood flow and the accumulation of IMP, which forms pools within the alveolar spaces of the cancerous areas. The image prepared with the remain rate revealed a hot image in the cancerous regions, even when this was not apparent in the delayed image. The remain rate image may therefore be useful in the identification of cancerous areas in lung tissue if it is used in comparison with the initial image.

Adult↗
PubMed1995

Effect of poly(ADP-ribose) synthetase on the expression of major histocompatibility complex (MHC) class II genes.

We have studied the effect of poly(ADP-ribose) synthetase on the interferon-gamma (IFN-gamma)-inducible expression of major histocompatibility complex (MHC) class II molecules. We constructed an expression plasmid capable of expressing either a sense RNA (MT-ARS) or an antisense RNA (pAS-FL or pAS-5') for poly(ADP-ribose) synthetase. We transfected the plasmid into mouse or human macrophage tumor cells and examined the effect on the expression of MHC class II molecules. The IFN-gamma-inducible expression of MHC class II gene was considerably reduced in transformant clones (A-2, B-2), in which the synthetase was highly expressed, whereas the depletion of the synthetase due to the expression of antisense RNA for the synthetase amplified the expression of MHC class II molecules. The results indicate that the level of the synthetase critically regulates the IFN-gamma-inducible MHC class II molecules. Next, we analyzed DNase I hypersensitive sites (DHS) of mouse MHC class II, I-A beta gene and found two sites, one in the promoter region and the other one in the first intron. The DHS in first intron was less sensitive towards DNase I attack in transformant clones (A-2, B-2) in which the synthetase was synthesized in a large quantity. Thus we constructed two beta-galactosidase reporter genes, one (A beta 2.0kb-lac z) containing the promoter region to a part of the second exon of the class II gene, and the other (A beta pro-lac z) containing the promoter region of the class II gene alone. The expression of the reporter gene was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) and found that the expression of A beta 2.0kb-lac z was suppressed in the transformant clones (A-2, B-2) relevant to control cells but the expression of A beta pro-lac z was the same level among those cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

IL-2 signaling: recruitment and activation of multiple protein tyrosine kinases by the components of the IL-2 receptor.

Cytokine receptors transduce signals to the cell interior upon binding of their cognate ligands, eventually leading to cellular responses such as cellular proliferation, differentiation and other effector functions. Most of the cytokine receptors, including the interleukin (IL)-2 receptor, consist of two or more distinct subunits, yet none possess any known catalytic activity such as protein tyrosine kinase activity. Significant advances have recently been made in identifying the multiple signaling molecules, including protein tyrosine kinases, that couple with the cytoplasmic regions of the IL-2 receptor, although their exact roles in cytokine signaling are still not fully understood. Another important development in the understanding of IL-2 signaling is the identification of the target genes, including nuclear proto-oncogenes. Furthermore, structure-function analyses of the components of the IL-2 receptor have enabled the dissection of multiple intracellular signaling pathways that lead to the induction of the respective target genes.

Animals↗
PubMed1995

Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway.

The IL-2 receptor (IL-2R) consists of three subunits, the IL-2R alpha, IL-2R beta, and IL-2R gamma chains. The IL-2-induced proliferative signals emanate from the cytoplasmic domains of IL-2R beta and IL-2R gamma, but the nature and function of the signaling molecules that transmit these signals are not fully understood. Here, we report that Syk protein tyrosine kinase (PTK) is physically associated with IL-2R in peripheral blood lymphocytes. cDNA expression studies further revealed that this association is critical for the IL-2-induced activation of Syk PTK, which occurs primarily via the serine-rich region of the IL-2R beta chain, which is essential for proliferative signal transmission. Furthermore, we provide evidence that in the hematopoietic cell line, BAF-B03, the activation of Syk PTK results in the induction of the c-myc gene, an event critical for the cell proliferation. Thus, Syk PTK may be a critical integral member of the signaling molecules engaged by the IL-2R.

Adult↗
PubMed1995

Alteration of phospholipase C-delta protein level and specific activity in Alzheimer's disease.

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. We have previously demonstrated that an antibody to an isozyme of PLC, PLC-delta, produced intense staining of neurofibrillary tangles in the brains of patients with Alzheimer's disease. In the present study, we investigated the protein level and activity of this enzyme in control and Alzheimer brains. Western blot analysis using a specific antibody for PLC-delta showed that the concentration of PLC-delta protein was significantly higher in the cytosolic fraction of Alzheimer disease cortical tissue than in control brains. The activity of PLC-delta, which hydrolyzes phosphatidylinositol, was also investigated, and we found that PLC-delta activity was not significantly different in the Alzheimer and control cytosolic fractions. These results indicate that the specific activity of PLC-delta is decreased in Alzheimer brains and suggest that inactivation of PLC-delta might be related to the pathophysiology of this disease.

Aged↗
PubMed1995

Detection of monocyte chemotactic and activating factor (MCAF) and interleukin (IL)-6 in human seminal plasma and effect of leukospermia on these cytokine levels.

PROBLEM: To demonstrate whether monocyte chemotactic and activating factor (MCAF) and interleukin-6 (IL-6) are present in the seminal plasma, and whether these presence is modulated by leukospermia. METHODS: Semen samples from 53 men were obtained by masturbation and examined for the presence of MCAF and IL-6 by enzyme immunoassay (EIA). Semen samples were obtained from 28 infertile men without leukospermia, 16 infertile men with leukospermia, and nine proven-fertile men. The correlation between the amount of MCAF in the seminal plasma with some spermiogram parameters and other cytokines such as IL-6 and IL-8 was statistically evaluated. RESULTS: Immunoreactive MCAF was detected in the seminal plasmas of all 53 subjects. The MCAF titer in the seminal plasma of patients with leukospermia (11.19 +/- 2.75 micrograms/l) was significantly higher than that in the seminal plasma of the patients without leukospermia (3.24 +/- 0.53 micrograms/l) and the fertile men (2.78 +/- 0.35 micrograms/l) (P < 0.001). The IL-6 titer in the seminal plasma of the patients with leukospermia (21.05 +/- 4.49 ng/l) was also significantly higher than that in the seminal plasma of the patients without leukospermia (8.77 +/- 1.92 ng/l) and the fertile men (6.94 +/- 1.27 ng/l) (P < 0.01). There was a high degree of correlation among the levels of MCAF, IL-6 and IL-8 in the seminal plasma. CONCLUSIONS: These findings demonstrated the presence of MCAF and IL-6 in the seminal plasma, and that the levels of these cytokines were elevated in the seminal plasma of the infertile patients with leukospermia.

Chemokine CCL2↗
PubMed1995

Sequencing of the gene encoding the major pilin of pilus colonization factor antigen III (CFA/III) of human enterotoxigenic Escherichia coli and evidence that CFA/III is related to type IV pili.

The plasmid-encoded structural gene cofA necessary for the production of the major pilin subunit of pilus colonization factor antigen III (CFA/III) of human enterotoxigenic Escherichia coli was identified, and the nucleotide sequence of the gene was determined. cofA consists of 714 nucleotides encoding a 238-amino-acid protein (molecular weight of 25,309). CofA seems to be a precursor of CFA/III pilin, because the first 23 residues of the N-terminal amino acid sequence of the purified CFA/III pili coincided with the deduced amino acid sequence for residues 32 to 54 of CofA. Western blot (immunoblot) analysis of CofA also indicated its processing to form mature pilin in the presence of the downstream region of cofA. These results suggest that the major pilin of CFA/III pili is produced as a precursor form which is posttranslationally modified to the mature pilin and forms morphological pili after cleavage of the Gly-30-Met-31 junction, probably by a protease encoded by an as-yet-unknown gene located downstream of cofA. Interestingly, the N-terminal 30-amino-acid sequence of mature CFA/III shows the highest identity (76.7%) to TcpA pilin of Vibrio cholerae, which is a type IV class B pilin.

Antigens, Bacterial↗