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Biomedical subjects

Y Takiguchi

Publications and source records attributed to Y Takiguchi.

At least 55 records · Page 3Linked to original sources
PubMed1997

A novel peptide motif for platelet fibrinogen receptor recognition.

To develop a specific antagonist of platelet alphaIIbbeta3 using small linear peptides, we synthesized a series of hexapeptides that did not have an Arg-Gly-Asp (RGD) sequence and examined their anti-platelet activity and their specificity for alphaIIbbeta3. We found a novel motif sequence, Pro-X1-X2-X3-Asp-X4, where X1 to X4 were all L-form alpha-amino acids, which specifically inhibited aggregation of human platelets at submicromolar concentrations. The Pro residue at the N terminus was essential to the anti-platelet activity, and the acetylation of the imino group of this residue also resulted in the complete loss of the activity. The results of the binding assay using purified human platelet alphaIIbbeta3 and placental alphavbeta3 and those of the cell adhesion assay suggest that this motif peptide is highly specific for platelet alphaIIbbeta3 among other integrins. Flow cytometric studies using an fluorescein isothiocyanate-labeled RGD peptide showed that this motif peptide inhibited the binding of an RGD peptide to activated platelets, suggesting that it has the same inhibitory mode as RGD peptides. Conformational analysis of this motif peptide and an RGD-containing peptide suggests that the imino group of the Pro residue may substitute for the role of the guanidino group of the Arg residue of the RGD sequence.

Animals↗
PubMed1997

Comparison of the promoters of the mouse (APEX) and human (APE) apurinic endonuclease genes.

We investigated the minimal promoter of APEX, which encodes mouse apurinic DNA repair endonuclease. A 1.85-kb fragment with APEX upstream sequences and approximately 290 bp of the transcribed region linked to a chloramphenicol acetyltransferase (CAT) reporter gene was assayed by transient transfection in NIH-3T3 cells. The minimal APEX promoter was comprised of approximately 190 bp of upstream and approximately 170 bp of transcribed DNA (exon 1 and most of intron 1). This approximately 360-bp region contains two CCAAT boxes and other consensus protein binding sites, but no TATA box. Deletion of the 5'-most CCAAT box decreased activity approximately 5-fold. The second CCAAT box (situated in exon 1) may play an independent role in APEX expression. Transcription start sites have been identified downstream of the second CCAAT box, and DNase I footprinting demonstrated NIH-3T3 nuclear proteins binding this region, including an Spl site located between the CCAAT boxes. Electrophoretic mobility-shift assays indicated binding by purified Sp1. Mouse proteins did not bind three myc-like (USF) sites in the APEX promoter, in contrast to the APE promoter. The APEX and APE promoter had similar activity in Hela cells, but in mouse cells, the murine promoter had approximately 5-fold higher activity than did the human promoter. Both the APEX and APE promoters exhibited bidirectional activity in their cognate cells.

3T3 Cells↗
PubMed1997

Effect of chitosan on renal function in patients with chronic renal failure.

The effects of chitosan have been investigated on eighty patients with renal failure undergoing long-term stable haemodialysis treatment. The patients were tested after a control treatment period of 1 week. Half were fed 30 chitosan tablets (45 mg chitosan/tablet) three times a day. Ingestion of chitosan effectively reduced total serum cholesterol levels (from 10.14 +/- 4.40 to 5.82 +/- 2.19 mM) and increased serum haemoglobin levels (from 58.2 +/- 12.1 to 68 +/- 9.0 g L-1). Significant reductions in urea and creatinine levels in serum were observed after 4 weeks of chitosan ingestion. The feeling of physical strength, the appetite and the sleep of patients in the treatment group had improved significantly after 12 weeks of ingestion, compared with those of patients in the control group. During the treatment period, no clinically problematic symptoms were observed. These data suggest that chitosan might be effective treatment for renal failure patients, although the mechanism of the effect should be investigated further.

Administration, Oral↗
PubMed1997

Stiff-man syndrome associated with antecedent myasthenia gravis and organ-specific autoimmunopathy.

We describe a case of stiff-man syndrome accompanied by diabetes mellitus, Hashimoto's thyroiditis and the antecedent myasthenia gravis. The diagnosis of stiff-man syndrome was made based on not only clinical findings and the characteristic electromyographic pattern but also the presence of antibodies to glutamic acid decarboxylase in the serum and cerebrospinal fluid. Stiff-man syndrome is known to be associated with organ-specific autoimmunopathy including insulin-dependent diabetes mellitus. The present case is the first one that stiff-man syndrome was preceded by myasthenia gravis of organ-specific autoimmunopathy. Stiff-man syndrome in the present case probably represents the one of fully expressed manifestations from the broad spectrum of organ-specific autoimmunopathy caused by the loss of self-tolerance.

Adult↗
PubMed1997

[Bronchial lipoma removed with bronchoscopic snaring forceps].

A 62-year-old woman was admitted to the hospital because of dyspnea. A chest X-ray film showed a massive left pleural effusion. Thoracentesis was done and purulent fluid was found. Streptococcus intermedius was detected in the fluid. Chest drainage and administration of antibiotics were successful, but computed tomography of the chest revealed a mass in the left main bronchus. The mass was removed with transbronchial electrosurgical snaring forceps and was found to be a lipoma. This tumor had low CT numbers (from -70 HU to -140 HU), and this finding may be useful in the differential diagnosis of endobronchial tumors.

Bronchial Neoplasms↗
PubMed1997

[Alveolar hemorrhage and glomerulonephritis in two patients with anti-neutrophil cytoplasmic antibodies].

A 55-year-old woman and a 56-year-old woman were admitted to the hospital because of dyspnea on exertion and bloody sputum. Chest roentgenography and computed tomography showed bilateral infiltrative shadows. Examination of bronchoalveolar lavage fluid and of specimens obtained by transbronchial lung biopsy revealed alveolar hemorrhage and hemosiderin-laden macrophages. Examination of specimens obtained by needle biopsies of the kidneys showed glomerulonephritis. Test for anti-neutrophil cytoplasmic antibody (ANCA) were positive; alveolar hemorrhage and glomerulonephritis accompanied by ANCA-related vasculitis was diagnosed. The patients' condition improved with administration of prednisolone and cyclophosphamide. Measurement of ANCA was useful for monitoring the activity of the disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

[Inflammatory bronchial polyps with a foreign body-like substance].

A 68-year-old male complaining of hemosputum was admitted to our hospital. Fiberoptic bronchoscopic examinations revealed bronchial polyps and a flat foreign body-like substance in the left main bronchus. A closer inspection of a biopsied bronchial inflammatory polyp showed inflammatory edema with hypervascularization in the submucosal space and inflammatory cell infiltration. Following complete removal of this foreign body-like substance, the polyps disappeared within six weeks. It is therefore feasible to assume that the polyps appeared as a reaction to this extrinsic substance. The origin of the foreign matter is not obvious because the patient had no history of aspiration and because the histological examination did not confirm that it was a foreign body. The substance could have been formed out of the organization and calcification of some secretes in the bronchus.

Aged↗
PubMed1996

The selective endothelin ETA receptor antagonist FR139317 inhibits neointimal thickening in the rat.

Endothelin is known as a potent mitogenic mediator. We tested the in vivo ability of FR139,317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro- 1H-azepinyl)]carbonyl]amino-4-methylpentanoyl] amino-3-[3-(1-methyl-1 H-indoyl)]propionyl]amino-3-(2-pyridyl)propionic acid), a selective antagonist of the endothelin ETA receptor subtype, to inhibit neointimal thickening following photochemically induced injury of the endothelium of rat femoral artery. FR139,317 (32 mg/kg s.c., twice a day) was administered for 3 weeks after the injury. FR139,317 significantly decreased the neointimal area (76.3%) without changing the medial area. Therefore, it is suggested that endothelin may play an important role, via mainly endothelin ETA receptors, in neointima formation in injured artery.

Animals↗
PubMed1996

Genomic structure and chromosomal assignment of the mouse Ku70 gene.

DNA-dependent protein kinase (DNA-PK) consists of three polypeptide subunits: Ku70, Ku80, and the DNA-PK catalytic subunit (DNA-PKcs). Mammalian mutants deficient in either Ku80 or DNA-PKcs function have been shown to be lacking in DNA double-strand break repair and V(D)J recombination, respectively. The precise role of the Ku70 gene in this process has not yet been determined, in part because no cell lines, animals, or human diseases involved with deficiencies in this gene have yet been identified. Both the human and the mouse Ku70 cDNAs have been cloned, and the human gene has been mapped to chromosome 22q13. The original mouse cDNA clones, however, lacked a complete 5'-region, and none of the mammalian Ku70 genomic sequences have been characterized. This report contains an analysis of the 5'-region of the mouse cDNA sequence, a characterization of the mouse Ku70 genomic structure, and fluorescence in situ hybridization data that map the mouse gene to chromosome 15. The deduced amino acid sequence of the mouse gene consists of 608 amino acids compared to 609 for the human gene. The genomic sequence is 24 kb and consists of 13 exons, including an untranslated first exon. Sequences from the upstream region of exon 1 revealed four consensus GC box sequences and a strong transcription initiation site at a reasonable location. The assignment of the mouse Ku70 gene to chromosome 15 is consistent with the syntenic relationship of this gene in human (chromosome 22q13) and mouse and adds to the comparative mapping data for the genes involved in the SCID phenotype.

Animals↗
PubMed1996

A chemiluminescent detection of superoxide radical produced by adherent leucocytes to the subendothelium following thrombolysis: studies with a photochemically induced thrombosis model in the guinea pig femoral artery.

Reocclusion following thrombolysis is a major limitation of thrombolytic therapy with recombinant tissue-type plasminogen activator (rt-PA) because denuded vessel wall exposed to blood following thrombolysis is a favourable surface for platelet and leucocyte deposition. We have applied a chemiluminescence technique to detect superoxide radical (0(-2)) produced by leucocytes adherent to the femoral artery 24 h after photochemically induced thrombogenesis in the guinea pig in vivo and subsequent thrombolysis by rt-PA. Intravenous administration of MCLA, a specific chemiluminescence reagent for detecting O(-2), markedly increased photon emission. the photon emission was markedly potentiated by phorbol myristate acetate and was suppressed by superoxide dismutase. Reocclusion 24 h after rt-PA induced thrombolysis was observed in 10 of 16 animals. Histological observations revealed extensive polymorphonuclear leucocytes adherent to the vessel wall at the site of thrombogenesis and thrombolysis. A higher level of 0(-2) could be detected from the arteries in which thrombolysis was induced compared with those without thrombolysis. Further, the level 0(-2) detected was greater in reoccluded arteries compared with those in which reflow was established. These observations suggest that 0(-2) is produced by adherent leucocytes at the site of thrombolysis and that leucocytes are involved in reocclusion after thrombolysis.

Animals↗
PubMed1996

A comparative study of the antithrombotic effect of aurintricarboxylic acid on arterial thrombosis in rats and guinea pigs.

1. The antithrombotic effect of aurintricarboxylic acid (ATA) which inhibits binding of von Willebrand factor (vWF) to platelet glycoprotein lb (GPlb) receptor was evaluated in photochemically-induced thrombosis models in the femoral artery of rats and guinea-pigs. 2. ATA at a dose of 10 mg kg-1 significantly prolonged the time required for thrombotic occlusion of the artery in rats. The antithrombotic efficacy was associated with a significant inhibition of platelet retention and ex vivo botrocetin-induced platelet aggregation. 3. On the other hand, in guinea-pigs, ATA at the same dose inhibited the platelet retention and the platelet aggregation, but did not prevent thromboocclusion. 4. ATA inhibited aggregation of washed platelets from rats or guinea-pigs in response to botrocetin and thrombin in a dose-dependent manner (1-30 microM), and to the same extent. 5. ATA moderately increased activated partial thromboplastin time and bleeding time in both species. 6. These results indicate that vWF may play a role in the development of occlusive arterial thrombosis in the rat, but not in the guinea-pig. 7. The antithrombotic activity of ATA may partly arise from its inhibitory effect on thrombin, in addition to that on the vWF-GPlb pathway

Animals↗
PubMed1996

Quality of life and anxiety before and after lung cancer chemotherapy: relationship to patient's personality.

The purpose of the study was to assess the quality of life (QOL) and anxiety in 50 inpatients with primary lung cancer and examine the influence of their personalities on the QOL assessment. We used a psychological personality test to evaluate the patient's personality, then followed the course of QOL and anxiety before and after chemotherapy. To measure QOL, we used Holmes's QOL checklist, and the State-Trait Anxiety Inventory was adopted to estimate the patient's anxiety. Eighty courses of chemotherapy were administered, and QOL evaluations were performed 235 times. By using factor analysis, the somatic, social and psychological factors were extracted which confirmed the reliability and validity of the QOL checklist. The psychological QOL score showed a correlation with A (Adult) and AC (Adapted Child) of the five ego states in the Egogram. Therefore, it is important to survey the patients' personalities in order to grasp their QOL accurately.

Adult↗
PubMed1995

Early administration of YT-146, an adenosine A2 receptor agonist, inhibits neointimal thickening after rat femoral artery endothelium injury.

Adenosine is known to inhibit vascular smooth muscle cell proliferation in vitro via adenosine A2 receptor activation. We tested the inhibitory effect of an adenosine A2 receptor agonist, 2-octynyladenosine (YT-146), on in vivo intimal thickening following a photochemically induced injury of the endothelium of rat femoral artery. YT-146 (1 mg/kg/day) was administered s.c. for the first 3, 7 or 28 days after the injury. YT-146 significantly decreased neointimal area and the ratio of intima to medial area measured 28 days after the injury, regardless of the duration of administration. These results suggest that YT-146 may inhibit the early events of neointimal formation. The effect is long lasting and is not reversed even if YT-146 is stopped after a short course of administration.

Adenosine↗
PubMed1995

Evaluation of metastatic ability at specific times during primary tumor growth: a novel spontaneous metastasis assay.

A transformed NIH 3T3 fibroblast cell line, Cl-e, normally does not produce spontaneous metastasis from subcutaneous or footpad tumors in nude mice. However, pulmonary tumor nodules are formed when more than 1 x 10(3) cells are injected intravenously into nude mice. Co-injection of 1 x 10(6) heavily irradiated and inactivated cells increases the clonogenic ability of the viable cells in that tumor colonies then occur with as few as 1 x 10(2) viable cells. Utilizing the action of these inactivated cells to enhance the lung colonizing ability of a relatively small number of viable tumor cells, we have developed a novel experimental model of spontaneous metastasis. In this model, a footpad tumor of the nude mouse metastasizes to the lungs following intravenous injection of 1 x 10(6) inactivated cells at a specific time of tumor growth and following tumor foot amputation, whereas no spontaneous metastasis develops without injection of inactivated cells. This model enables us to detect metastatic ability which would otherwise be too low to detect using other assays. In addition, it allows us to evaluate metastatic ability at a specific time point during primary tumor growth, since no metastases can develop during the periods before inactivated cell injection and after tumor amputation. Using this model, we have determined that the metastatic ability of Cl-e tumors in the footpad is constant throughout the exponential and stationary growth phases, even though cells isolated from exponentially growing tumors possess a 3.3-fold greater lung colonizing ability following intravenous injection than those from stationary tumors. This new experimental model may be applicable to other tumor cell lines and to other analyses where metastatic ability during a defined interval of tumor growth is of importance.

3T3 Cells↗
PubMed1995

Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model.

1. The antithrombotic effect of a new specific thrombin inhibitor, CX-397, was examined in a photochemically-induced arterial thrombosis model in the rat femoral artery and compared with that of heparin. 2. Pretreatment with CX-397 (10, 20 and 40 micrograms kg-1 min-1, i.v.) from 15 min before the experiment prolonged the time required for thrombotic occlusion of the artery in a dose-dependent manner. The antithrombotic efficacy of CX-397 was associated with modest increases in activated partial thromboplastin time (APTT) and template bleeding time. 3. On the other hand, heparin at a dose of 450 micrograms kg-1 markedly prolonged APTT and the bleeding time, but did not inhibit thrombo-occlusion. 4. CX-397 selectively inhibited platelet aggregation and concurrent secretion of 5-hydroxytryptamine (5-HT) and thromboxane A2 (TXA2) production from platelets in response to thrombin, but not to collagen and ADP, in a dose-dependent manner (5-100 ng ml-1). 5. CX-397 at 10 micrograms kg-1 combined with vapiprost, a TXA2 receptor antagonist, at 0.1 mg kg-1 significantly prevented occlusion, whereas, at these doses, neither drug alone had much effect. 6. These results demonstrate that CX-397 may prove to be more efficient for preventing platelet-rich thrombosis than heparin. Thrombin may play an important role in the rat thrombosis model. 7. The additive antithrombotic effect of the combination of thrombin inhibitor and TXA2 receptor antagonist at low doses suggests that thrombin and TXA2 may work in concert to produce thrombosis.

Animals↗
PubMed1995

Comparison of antithrombotic effects of GPIIb-IIIa receptor antagonist and TXA2 receptor antagonist in the guinea-pig thrombosis model: possible role of TXA2 in reocclusion after thrombolysis.

The effects of Ro 44-9883, a new specific antagonist of platelet glycoprotein IIb-IIIa receptor, on thrombus formation and reocclusion after thrombolysis induced by tissue-type plasminogen activator (t-PA) were compared with those of vapiprost, a thromboxane (TX) A2 receptor antagonist, using a photochemically-induced thrombosis model in the guinea-pig femoral artery. Pretreatment with Ro 44-9883 (5, 10 and 20 micrograms/kg/min, i.v.) prolonged the time required to occlude the artery in a dose-dependent manner. Ro 44-9883 at 10 and 20 micrograms/kg/min significantly inhibited ex vivo platelet aggregation in whole blood induced by collagen, ADP or U46619. Vapiprost 0.3 mg/kg inhibited thrombus formation and platelet aggregation induced by collagen or U46619, to the same extent as Ro 44-9883 at the higher doses. In the thrombolysis study, Ro 44-9883 at the higher doses given as comedication with t-PA reduced the time to achieve reperfusion and increased the vascular patency after successful reperfusion. Vapiprost also significantly reduced the time to reperfusion and prevented reocclusion. However, the vascular patency after thrombolysis by t-PA with vapiprost was significantly increased compared with Ro 44-9883. Ro 44-9883 inhibited platelet aggregation, but did not prevent TXA2 formation in platelets. Thus, vascular contraction mediated by platelet-derived TXA2 may be responsible for lower efficacy of Ro 44-9883 against reocclusion compared with vapiprost. These results indicate that not only platelet aggregation but also vasoconstriction may contribute to reocclusion after t-PA-induced thrombolysis in the guinea-pig.

Acetates↗
PubMed1995

[Wilson-Jones type angiosarcoma with marked response to intrapleural administration of interleukin-2].

A 64-year-old woman was admitted to our hospital with a hemothorax after one year of therapy for angiosarcoma that had arisen from the skin of the head. The hemothorax was believed to have resulted from metastasis of the angiosarcoma. Interleukin-2 (IL-2) at a dose of 20 x 10(4) U once daily was administered intrapleurally. Clinical improvement was first observed on the second day after the first dose of IL-2. Increases in natural and in lymphokine-activated killer activity of lymphocytes in pleural effusion were found on the eighth day. Starting on the 16th day of IL-2 therapy, no more fluid was drained, so administration of IL-2 was stopped. The clinical course indicated that the pleural effusion disappeared not because of pleurodesis but because of the anti-cancer effects of IL-2. There were no marked side effects, and intrapleural administration of IL-2 may be useful in patients with hemothorax due to metastasis of angiosarcoma.

Female↗