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Biomedical subjects

S Taniguchi

Publications and source records attributed to S Taniguchi.

At least 181 records · Page 10Linked to original sources

Expression of vascular endothelial growth factor and its receptors during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine in rats.

The expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), VEGFR-1/Flt-1 and VEGFR-2/Flk-1, was investigated by immunohistochemical and northern blot analysis during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats. After BHP was given in the drinking water for 12 wk, the rats were maintained without further treatment until they were killed at 20-28 wk. Immunohistochemical studies revealed VEGF expression in almost all malignancies, the reaction being strongly positive in most adenocarcinomas (15 of 18; 83.3%) and squamous cell carcinomas (four of five; 80.0%), but less so in a total of 120 adenomas and 136 alveolar hyperplasias. In addition, VEGF mRNA and VEGFR mRNAs were found to be overexpressed in most adenocarcinomas and squamous cell carcinomas as well as in one to three of the five adenomas tested. The results indicated that VEGF and VEGFRs play important roles in the acquisition of malignant potential by preneoplastic lung lesions induced by BHP in rats. Moreover, overexpression of VEGF was related to upregulation of VEGFR-1/Flt-1 and VEGFR-2/Flk-1 expression in malignant and premalignant lung lesions.

Adenocarcinoma↗

[Myelodysplastic syndrome after autologous peripheral blood stem cell transplantation for adult acute myelogenous leukemia].

A 65-year-old woman was admitted to our hospital with arthritis and agranulocytosis. She had given a diagnosis of acute myelogenous leukemia (FAB classification M1) a year ago and treated with 3 cycles of cytarabine and anthracycline or etoposide for 4 months, achieving complete remission state. Her bone marrow aspirate revealed normocellularity with normal karyotype (46, XX [20]) without apparent dysplastic feature at this time. She received autologous peripheral blood stem cell transplantation subsequently after conditioning regimen consisted of granulocyte colony-stimulating factor, busulfan, Ara-C and etoposide. Three months later, she started to manifest low grade fever, polyarthralgia and agranulocytosis and she admitted to our hospital after nine months. Bone marrow aspirate revealed marked hypocellularity with dysplastic features in three series of hematopoietic cells. Arthritis was dramatically improved after administration of prednisolone, but low granulocyte count continued. Bone marrow aspirate revealed karyotypic abnormality with monosomy 7 and we diagnosed her as myelodysplastic syndrome. Chemotherapy-induced myelodysplasia has been reported so far. This case would represent secondary myelodysplastic syndrome after chemotherapy. We could not clarify the etiology for polyarthritis but could be one of the paraneoplastic syndrome. We should note subsequent occurrence of myelodysplasia when planning treatment schedule.

Aged↗

Enhanced expression of Tie2, its ligand angiopoietin-1, vascular endothelial growth factor, and CD31 in human non-small cell lung carcinomas.

Expression of angiogenesis-associated genes was compared in 32 primary non-small cell lung carcinoma samples (14 adenocarcinomas, 17 squamous cell carcinomas, and 1 large cell carcinoma) and paired adjacent noncancerous lung tissues using a multiprobe RNase protection assay. Levels of Tie2, angiopoietin (Ang)-1, vascular endothelial growth factor (VEGF), and CD31 mRNAs were higher in cancers than in adjacent noncancerous tissues, in contrast to the fms-like tyrosine kinase (Flt)-1, Flt-4, Tie1, thrombin receptor, endoglin, and VEGF-C, for which no differences were evident. Overexpression did not seem to differ with histological type and pathological stage. Significant positive correlations were found between mRNA expression of Ang-1 and those of Tie2 and CD31, and that of VEGF and those of Flt-1 and CD31. These findings suggest that Ang-1 and VEGF are important angiogenic factors in human non-small cell lung carcinomas.

Adult↗

[Re-coronary artery bypass grafting using a MIDCAB technique in a patient with a patent RITA-LAD graft].

In a patient with a patent RITA-LAD (right internal thoracic artery-left anterior descending artery) graft, re-CABG (re-coronary artery bypass grafting) with re-median sternotomy has been a high risk procedure. A 56-year-old male underwent 4-CABG (RITA-LAD, LITA-Dx, SVG-PL, and SVG-RCA) nine years ago. Coronary angiography showed that the RITA-LAD graft was well patent, but there was 95% stenosis distal to RITA-LAD anastomosis site. We performed re-CABG (right gastroepiploic artery-LAD; RGEA-LAD), using MIDCAB (minimally invasive direct coronary artery bypass) technique with neither re-median sternotomy nor cardiopulmonary bypass. The right gastroepiploic artery was harvested through a small upper median laparotomy and anastomosed to LAD through a small left anterior thoracotomy. The postoperative course was uneventful. This technique seems to be useful for re-revascularization of the LAD in a patient with a patent RITA-LAD graft.

Coronary Artery Bypass↗

Differences in the electrophysiological response to I- and the inhibitory anions SCN- and ClO-4, studied in FRTL-5 cells.

The electrophysiological properties of the Na+/I- symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN- than with I-. The reversal potential for I- and SCN- induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I- and SCN- translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with ClO-4 indicating that ClO-4 was either not transported into the cell, or the translocation was electroneutral. ClO-4 addition, however, did reverse the inward currents induced by I- or SCN-. These effects of I-, SCN- and ClO-4 on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN- in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN- produced an increasingly greater outward current. This outward current was transient. In addition, when SCN- was washed off the cells a transient inward current was detected. Unlike SCN-, 1-10 mM I- had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN- translocation system in addition to the SCN- translocation by the I- porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I-, SCN- and ClO-4 in thyroid cells.

Animals↗

Ethidium bromide-induced inhibition of mitochondrial gene transcription suppresses glucose-stimulated insulin release in the mouse pancreatic beta-cell line betaHC9.

Recently, a mitochondrial mutation was found to be associated with maternally inherited diabetes mellitus (Kadowaki, T., Kadowaki, H., Mori, Y., Tobe, K., Sakuta, R., Suzuki, Y., Tanabe, Y, Sakura, H., Awata, T., Goto, Y., Hayakawa, T., Matsuoka, K., Kawamori, R., Kamada, T., Horai, S., Nonaka, I., Hagura, R., Akanuma, Y., and Yazaki, Y. (1994) N. Engl. J. Med. 330, 962-968). In order to elucidate its etiology, we have investigated the involvement of mitochondrial function in insulin secretion. Culture of the pancreatic beta-cell line, betaHC9, with low dose ethidium bromide (EB) (0.4 microg/ml) for 2-6 days resulted in a substantial decrease in the transcription level of mitochondrial DNA (to 10-20% of the control cells) without changing its copy number, whereas the transcription of nuclear genes was grossly unaffected. Electron microscopic analysis revealed that treatment by EB caused morphological changes only in mitochondria and not in other organelles such as nuclei, endoplasmic reticula, Golgi bodies, or secretory granules. When the cells were treated with EB for 6 days, glucose (20 mM) could no longer stimulate insulin secretion, while glibenclamide (1 microM) still did. When EB was removed after 3- or 6-day treatment, mitochondrial gene transcription recovered within 2 days, and the profiles of insulin secretion returned to normal within 7 days. Studies with fura-2 indicated that in EB-treated cells, glucose (20 mM) failed to increase intracellular Ca2+, while the effect of glibenclamide (1 microM) was maintained. Our system provides a unique way to investigate the relationship between mitochondrial function and insulin secretion.

Animals↗

Intravenous infusion of Galalpha1-3Gal oligosaccharides in baboons delays hyperacute rejection of porcine heart xenografts.

BACKGROUND: Hyperacute rejection (HAR) of pig-to-primate discordant xenografts is caused by the deposition of preexisting natural antibodies that recognize Galalpha1-3Gal (alphaGal)-terminating oligosaccharides on glycoproteins and glycolipids, followed by complement-mediated lysis of the graft's endothelium. In vitro, these natural xenoantibodies can be blocked by alphaGal-containing oligosaccharides. We undertook in vivo pig-to-baboon cardiac xenotransplantation experiments to evaluate free oligosaccharides as inhibitors of HAR. METHODS: Initial 15-min intravenous infusions of alphaGal-oligosaccharides into baboons were used to measure pharmacokinetic parameters, and to assess the extent of neutralization of anti-alphaGal antibody activity. AlphaGal trisaccharide (Galalpha1-3Galbeta1-4GlcNAc) or pentasaccharide (Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc ) was administered at 0.5 mmol/kg into baboons. Next, two baboons that received porcine heterotopic heart xenografts were continuously infused with alphaGal pentasaccharide for 4-5 hr, maintaining the serum oligosaccharide concentration in the millimolar range. RESULTS: Pharmacokinetic analysis indicated that the oligosaccharides were rapidly cleared from the blood, with a serum half-life of 50 min. In the period during which blood oligosaccharide concentration was above 1 mM, as determined by high-pressure liquid chromatography, the serum cytotoxic activity against porcine cells was completely abolished. HAR of the xenograft was inhibited during the infusions, although there was some histological and immunohistological evidence of antibody-mediated injury on biopsies taken at the end of this period. CONCLUSIONS: Intravenous alphaGal oligosaccharides, by inhibiting anti-alphaGal antibody activity, delay but do not abolish the onset of HAR.

Animals↗

Long-term benefits of internal thoracic artery-coronary artery bypass in Japanese patients.

OBJECTIVES: This study sought to determine the effects of grafting the internal thoracic artery (ITA) to the left anterior descending coronary artery (LAD) on long-term (10-year) survival, the cardiac death-free rate, and on the cardiac event-free rate in Japanese patients. BACKGROUND: The use of ITA grafts has been reported to enhance postoperative survival and to decrease the occurrence of cardiac events in the Western literature. However, the survival benefits in Japanese patients, who may have different prognoses with coronary artery disease and a different fate of a saphenous vein graft, have not yet been determined. SUBJECTS AND METHODS: A total of 954 consecutive patients who underwent coronary artery bypass graft operations (CABG) during the last 12 years at the Nara Medical University were followed and evaluated. Of these, 713 patients underwent ITA-CABG to at least the LAD (ITA group), and 241 patients received a saphenous vein graft (SVG) to the LAD (SVG group). At the time of operation, no significant difference was found between these two groups in age, sex ratio left ventricular ejection fraction, left ventricular end-diastolic pressure, cardiac index, incidence of unstable angina, or in the necessity for an emergency operation. However, those patients who received ITA-CABG had significantly higher incidences of diabetes mellitus, hyperlipidemia, and left main coronary artery disease. RESULTS: The 10-year cumulative graft patency rate for the LAD was 23% higher in the ITA group (90.3%) compared to the SVG group (67.0%), (p < .0001). Despite increased preoperative risk factors, patients in the ITA group showed significant improvements in their 5- and 10-year cumulative survival rates as well as in their cardiac death-free and event-free rates. Furthermore, this study demonstrated that ITA grafts improved the prognoses of patients with diabetes mellitus or left ventricular dysfunction and lowered both the long-term postoperative cardiac-death rate and the cardiac-event rate. CONCLUSIONS: The use of ITA grafts was effective in improving both the postoperative survival and cardiac event-free rates, and should be recommended in patients with diabetes mellitus or left ventricular dysfunction. ITA grafting to the LAD should be a routine operation in almost all categories of such patients.

Aged↗

Differential expression of moesin in cells of hematopoietic lineage and lymphatic systems.

Moesin is a member of the ERM family consisting of ezrin, radixin, and moesin. The protein is located in the plasma membrane similarly to ezrin and radixin, and is thought to regulate cellular movements and morphological changes. Using monoclonal antibody CR-22, the specificity of which against human moesin was confirmed by immunoprecipitation and western blotting analysis, we immunohistochemically stained various formalin-fixed and paraffin-embedded human tissues, in particular, clots of bone marrow and lymphatic tissues, to examine moesin expression in cells of hematopoietic lineage and lymphatic systems. In the bone marrow, moesin was expressed in myeloid cells, while little staining was detected in erythroid cells. Moesin was highly expressed in both the center and the periphery of mature megakaryocytes. In the lymphatic tissues, moesin was strongly expressed by T-lymphocytes in the paracortex. In the mantle zone, the periphery of the germinal center, moesin was expressed by small lymphocytes which were identified as B-lymphocytes. Furthermore, in areas of inflammation, moesin was expressed in both the center and the periphery of neutrophils, whereas in some neutrophils in distant areas, moesin was localized at the cellular periphery. These results suggest that differential expression of moesin in these cells is involved in their morphology and specialized functions.

Antibodies, Monoclonal↗

Gene transfer into the donor heart during cold preservation for heart transplantation.

BACKGROUND: Ex vivo gene transfer to heart grafts may hold promise as a means of changing alloreactivity or xenoreactivity after transplantation. However, it remains to be determined how effectively gene transfer can be accomplished within a short time in cold-stored grafts that are ready to be transplanted. METHODS: We performed an experimental study using a replication-defective adenovirus (Adex1CALacZ) encoding the Escherichia coli beta-galactosidase (beta-gal) gene to perform gene transfer to heart grafts awaiting transplantation. Thirty hearts of Wistar rats were removed and their coronary arteries were perfused with University of Wisconsin solution containing 1 x 10(9), 1 x 10(10), or 1 x 10(11) plaque-forming units of the recombinant adenovirus at 4 degrees C for 60 minutes. As a control, other hearts were perfused with University of Wisconsin solution with an adenoviral vector that did not contain the beta-gal gene (Adex1w1) for the same period. After perfusion, the grafts were implanted in the necks of syngeneic adult rats. The grafts were removed each week after transplantation and their expression of beta-gal was assessed by 5-bromo-4-chloro-3-indoyl-beta-D-galactoside staining. RESULTS: Successful gene transfer and expression of the beta-gal gene were demonstrated in adenovirus-perfused hearts. Gene transfer occurred preferentially in the cardiomyocytes over the endothelial cells and smooth muscle cells of the coronary vessels. In hearts perfused with 1 x 10(9) plaque-forming units of the adenovirus, gene expression persisted for 4 weeks after transfer, but it diminished gradually and was minimal by day 28. Histologic analyses revealed slight inflammatory reactions in the myocardium. In hearts perfused with 1 x 10(10) and 1 x 10(11) plaque-forming units of the adenovirus, beta-gal diminished 3 weeks after transplantation and a prominent infiltration of leukocytes was recognized in the myocardium. CONCLUSIONS: This study demonstrated that the cardiomyocytes of heart grafts express an exogenous gene product after adenovirus-mediated gene transfer under hypothermic preservation conditions. However, immune or inflammatory reactions to recombinant adenoviruses must be taken into account when a large number of adenoviruses are injected into the coronary arteries.

Adenoviridae↗

Tracheal replacement with cryopreserved tracheal allograft: experiment in dogs.

BACKGROUND: It has been difficult to perform tracheal allotransplantation without immunosuppression. To determine whether cryopreserved trachea can be used in tracheal replacement, we evaluated the viability of cryopreserved tracheal allografts in a canine model of immunosuppressant-free transplantation. METHODS: Cryopreserved tracheal allografts, which had been frozen to -80 degrees C in a programmed freezer and then stored in liquid nitrogen (-196 degrees C) (group 1, n = 6), fresh tracheal autografts (group 2, n = 5), and fresh tracheal allografts (group 3, n = 4) were transplanted into the thoracic segment of the trachea using an omental flap without immunosuppressive agents. RESULTS: All dogs in groups 1 and 2 survived, but in group 3, all 4 died of airway obstruction between 1 month and 2 months after operation. Histologically, the cryopreserved allografts displayed normal epithelium and cartilage, but the fresh allografts showed chronic inflammatory changes, no epithelium, and no cartilage. CONCLUSIONS: Cryopreserved tracheal allografts maintain their structural integrity after transplantation. The cryopreservation process seems to reduce the allogenic response of the trachea in canine models. Therefore, we believe the cryopreserved tracheal allograft is an excellent choice for tracheal replacement.

Airway Obstruction↗

The role of cellular motility in the invasion of human neuroblastoma cells with or without N-myc amplification and expression.

BACKGROUND/PURPOSE: Patients who have neuroblastomas with N-myc amplification that are extremely invasive and result in distant metastases tend to have a very poor prognosis. The authors reported previously that N-mycamplification and expression might be closely related to the invasiveness of human neuroblastoma cells. However, the role of cellular motility has not yet been clarified in the invasion of neuroblastoma cells. The aim of this study was, therefore, to elucidate the role of cellular motility in the invasion of neuroblastoma cells. METHODS: Six human neuroblastoma cell lines were used for an invasion assay in vitro using polycarbonate filters coated with basement membrane Matrigel. The amplification and expression of N-myc oncogene was examined by Southern and Northern blotting, respectively. The cellular motility was quantified by computerized image analysis on the morphology of cultured cells. RESULTS: IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a high degree of invasiveness and a high cellular motility, whereas NB-69 and SK-N-SH without N-myc amplification showed an extremely low degree of invasiveness and cellular motility. ST without N-myc amplification, which was established from an aggressive tumor, showed an exceptionally high degree of motility and invasiveness. A transcriptional reduction of the N-myc gene by retinoic acid (RA) decreased the motility, which thus resulted in a marked decline of invasiveness in IMR-32 and GOTO. CONCLUSION: The cellular motility correlated with the invasive capacity of human neuroblastoma cells, which thus indicated that cellular motility may play an important role in invasion.

Cell Movement↗

Difference in acetylcholine-induced nitric oxide release of arterial and venous grafts in patients after coronary bypass operations.

OBJECTIVES: In vivo investigation of nitric oxide release in coronary bypass grafts has not been reported. We studied acetylcholine-induced nitric oxide release in vivo of coronary bypass grafts and vasomotor responses to acetylcholine of grafted coronary arteries in patients after coronary bypass grafting. METHODS: We examined 24 internal thoracic artery grafts and 16 saphenous vein grafts in 39 patients. The mean ages of the patients were 65 years for the arterial grafts and 68 years for the venous grafts. Nitric oxide was measured as the plasma nitrite level by the Griess reaction. Before and after intragraft acetylcholine infusion (5 microg), blood was sampled from the distal end of the graft, and angiograms were taken and analyzed by cine-densitometry. RESULTS: The plasma nitrite concentration after stimulation with acetylcholine compared with the control value was 134%+/-52% at 4 minutes (p=0.05) and 184%+/-107% at 6 minutes (p=0.01) in the arterial grafts; in the venous grafts these values were 101%+/-24% at 4 minutes (p=0.96) and 108%+/-36% at 6 minutes (p=0.69). Low-dose acetylcholine dilated the coronary arteries supplied by arterial grafts by 6.3%+/-16.6% whereas coronary arteries supplied by venous grafts were reduced by 9.8%+/-11.8% in diameter and the vasoactive responses were different (p=0.01). CONCLUSIONS: In vivo internal thoracic artery grafts had more endothelium-derived nitric oxide release in response to acetylcholine than did saphenous vein grafts after coronary bypass grafting.

Acetylcholine↗

Epithelial regeneration and preservation of tracheal cartilage after tracheal replacement with cryopreserved allograft in the rat.

OBJECTIVE: We investigated the origin of the epithelium in transplanted cryopreserved tracheal allografts in rats and tried to clarify the mechanism by which immunogenicity is reduced in this procedure. METHODS: Tracheal transplantation was performed with PVG rats (allele at the RT1 locus: c) used as donors and ACI rats (allele at the RT1 locus: a) as recipients. After resection of a 5-ring segment of the cervical trachea of an ACI rat, the trachea was reconstructed with the cryopreserved tracheal segment of a PVG rat (n = 6). No immunosuppressive agents or steroids were given. Histologic changes were determined and immunohistochemical staining was performed to investigate major histocompatibility complex class I antigens of the transplanted tracheal segment. RESULTS: Two months after tracheal transplantation, 6 surviving ACI rats were killed. Histologically, the epithelium and tracheal cartilage of the transplanted cryopreserved segment displayed normal structure. Immunohistochemical staining showed that the major histocompatibility complex class I antigen of the ACI rat was expressed in the epithelium of the transplanted segment and that the class I antigen of the PVG rat was expressed in the cartilage of the transplanted segment. CONCLUSIONS: After transplantation of the cryopreserved trachea, the epithelium of the transplanted cryopreserved segment originated from the recipient epithelium whereas the cartilage retained the structure of the donor trachea. We hypothesize that transplantation of a cryopreserved trachea leads to the growth of the recipient's epithelium over the donor trachea, thereby reducing the antigenicity of the transplant.

Animals↗

Production of macrocyclic ellagitannin oligomers by Oenothera laciniata callus cultures.

Callus cultures of Oenothera laciniata grown on LS agar medium supplemented with IAA and kinetin produced large amounts of the macrocyclic ellagitannin dimer, oenothein B, and a trimer, oenothein A, accompanied with related monomeric hydrolysable tannins. The content of the main compound oenothein B (65 mg/g dry wt) in calli cultured on modified LS medium containing 10 mM NH4+ and 5 mM NO3- was nearly two times higher than that in intact leaves.

Biopolymers↗

Plasma levels of type II phospholipase A2 and nitrite/nitrate in patients with burns.

Type II phospholipase A2 (type II PLA2), nitrite/nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and endotoxin were studied in burn patients. Type II PLA2 values and NOx values were both significantly higher in the group that died, the group with shock as a complication and the group with multiple organ dysfunction syndrome (MODS) as a complication, than in the group that survived, the group without shock as a complication and the group without MODS as a complication, respectively. The results suggested that type II PLA2 and nitric oxide (NO) may play a major role in the pathology of burn patients. Significant correlations were found between TNF-alpha and type II PLA2 values and between type II PLA2 and NOx values, suggesting the possibility of involvement in each other's production.

Adult↗

Moesin and CD44 expression in cutaneous melanocytic tumours.

The ERM (ezrin, radixin and moesin) family members, located just beneath the plasma membranes, are thought to be involved in the association of action filaments with the plasma membrane. One of the family members, moesin, is reported to bind to CD44. Splice variants of CD44 are thought to be associated with tumour progression or differentiation. Our aim was to investigate immunohistochemically the expression of moesin together with CD44 on paraffin tissue sections of a series of melanocytic tumours. The material included 12 ordinary melanocytic naevi, six Spitz naevi, eight dysplastic naevi, six blue naevi, seven malignant melanomas in situ, 15 primary malignant melanomas, five metastatic melanomas to the skin and five lymph node metastases. In the normal skin and the melanocytic tumours the expression of moesin was largely similar to that of CD44 standard. Strong moesin staining was observed in benign melanocytic lesions and melanomas in situ. However, the expression was decreased in advanced malignant melanomas. The moesin labelling in melanoma cells was downregulated with the depth of dermal invasion. The immunoreactivity was also diminished in the skin metastases and the lymph node metastases of melanoma. These results suggest that in melanocytic tumours, the alternation in the expression of moesin may be involved in the progression of malignancy.

Adult↗