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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 109 records · Page 6Linked to original sources

[Bypass grafting of left subclavian artery to descending thoracic aorta for relative stenosis of bypass graft after total correction for type A IAA with VSD].

A 4-year-old child underwent one-stage total correction for type A IAA with VSD in 1975 as the first successful case in Japan. At age 21, a gradual rise in her upper limb pressure to 190 mmHg prompted repeat catheterization, which showed a pressure gradient across the EPTFE graft of 58 mmHg. Under general anesthesia in the right lateral position, the patient's left thorax was reopened. The EPTFE graft had undergone patchy calcific degeneration and was significantly hardened. An 18-mm Toray graft preclotted with fibrin glue was anastomosed to the left subclavian artery in side-to-end fashion. Its distal end was anastomosed to the descending aorta distal to the EPTFE bypass during a 20-minute aortic occlusion. The postoperative recovery was uneventful and the pressure gradient between the upper and lower limbs fell to 0 at discharge. We chose this method for reoperation of type A IAA and CoA because of the reduced need for dissection and better effectiveness.

Adult

Involvement of heterotrimeric GTP-binding protein and rho protein, but not protein kinase C, in agonist-induced Ca2+ sensitization of skinned muscle of guinea pig vas deferens.

We studied the involvement of protein kinase C (PKC) and a small GTP-binding protein (G-protein), rho, in receptor-mediated Ca2+ sensitization of the contractile apparatus of smooth muscle of guinea pig vas deferens. In beta-escin-permeabilized smooth muscle strips, norepinephrine (NE) in the presence of GTP caused further contraction of the preparations at a constant Ca2+ level (Ca2+ sensitization). Prazosin and GDP beta S, a nonhydrolyzable GDP analogue, inhibited NE-induced Ca2+ sensitization, indicating an alpha-1 adrenoceptor/G-protein mediated response. GTP alone (> 10 microM) and GTP gamma S, a non-hydrolyzable GTP analogue, also induced Ca2+ sensitization. Pretreatment of preparations with C3 exoenzyme of Clostridium botulinum, which is known to ADP-ribosylate rho family proteins, with NAD resulted in complete inhibition of NE- and GTP (GTP gamma S)-induced Ca2+ sensitization. AIF4-, which activates heterotrimeric G-, but not small G-protein also induced Ca2+ sensitization. Interestingly, AIF4(-)-induced Ca2+ sensitization was inhibited by not only GDP beta S but also C3-treatment, suggesting that activation of heterotrimeric GTP-binding protein precedes activation of rho protein. On the other hand, phorbol 12,13-dibutyrate, like NE, also induced Ca2+ sensitization. The sensitization was inhibited by PKC(19-31), a PKC inhibitor peptide. However, PKC(19-31) did not have any effect on NE- or AIF4(-)-induced Ca2+ sensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP Ribose Transferases

[Chemo- and endocrino-therapy of breast carcinoma xenografts in the dormant or exponential growth phase].

In case of concerning about recurrence case after operative treatment of breast cancer, we must suppose existence of dormant breast cancer cell. To elucidate a rational treatment of the breast cancer in the dormant stage, we have developed a new treatment model using human breast carcinoma xenografts (MCF-7, R-27 and Br-10) in nude mice. After the sc inoculation of the tumors, the treatment was initiated with or without the previous estradiol (E2) stimulation. While MCF-7 was sensitive to mitomycin C (6 mg/kg i.p.) and and tamoxifen pellet (2.5 mg/mouse s.c.) in the dormant and exponential growth phase, R-27 and Br-10 were sensitive to the drugs only in the exponential growth phase but not in the dormant stage. These results suggested that the sensitivity of human breast carcinoma cells in the dormant stage is rather low, however some strain would be also sensitive to the treatment. This model seems to be useful in evaluating the adjuvant therapy of breast carcinoma after surgery.

Animals

[Systemic and regional myocardial distribution of 123I-BMIPP in normal subjects].

We estimated the systemic and left ventricular (LV) regional myocardial distribution of 123I-BMIPP (beta-methyl-p-iodophenyl-pentadecanoic-acid) in normal subjects (n = 13, mean age 43.9). In planar studies, the count ratios of heart, lung and liver to mediastinum were 2.63, 1.28 and 3.80 in the early images, and 2.23, 1.20 and 2.26 in the delayed images, respectively. The uptake in liver was almost identical with that in heart in the delayed images. In SPECT studies, the regional relative counts in anterior, septal, posterior and lateral LV walls were 100, 98, 96 and 108 (%) in the initial images, and 100, 98, 99 and 107 (%) in the delayed images, respectively. The regional relative uptake was significantly higher in the lateral wall than those in the other parts of LV walls in both images. The relative counts in the basal, mid- and apical portions were 100, 111 and 87 (%) in the initial images, and 100, 113, 92 (%) in the delayed images, respectively. These results suggest that the myocardial regional distribution of BMIPP is not always uniform even in normal subjects. Thus, it is necessary to interpret with caution in the light of these findings, especially for detect in a myocardial lesion in an early phase of cardiomyopathy or a mild myocardial ischemia.

Adult

Functional expression of transporter for beta-lactam antibiotics and dipeptides in Xenopus laevis oocytes injected with messenger RNA from human, rat and rabbit small intestines.

A heterologous gene expression system, Xenopus laevis oocytes, was used to prove the intestinal absorption of various beta-lactam antibiotics mediated by an H(+)-dipeptide cotransport system in rat, rabbit and human small intestines. The microinjection of mRNA (messenger RNA) from rat intestine into Xenopus laevis oocytes led to significantly higher uptakes of p.o. active cephalosporins including zwitter-ionic derivatives (cephalexin, cephradine and cefadroxil) and dianionic derivatives (cefixime and ceftibuten) in comparison with oocytes injected with water, whereas the uptake of cefazolin, a parenterally administered derivative, was negligible in both mRNA- and water-injected oocytes. The uptake of cefadroxil was reduced significantly in the presence of dipeptide and various beta-lactam antibiotics, but not in the presence of an amino acid. After sucrose density gradient centrifugation of mRNA, the highest expression of transport activities of both cefadroxil and ceftibuten was observed in the same mRNA fraction with a size of 2.20 to 3.75 kilobases. mRNA-injected oocytes showed a marked pH-dependency in the uptakes of cefadroxil and ceftibuten, whereas water-injected oocytes exhibited only modes uptakes. The most stimulated uptakes of cefadroxil and ceftibuten were observed at an external pH of 5.5 and 5.0, respectively. Furthermore, injection of mRNA isolated from either rat rabbit or human small intestine into oocytes produced significantly higher uptake of cefadroxil and ceftibuten compared with those by oocytes injected with water. Thus, intestinal absorption of p.o. active beta-lactam antibiotics was confirmed to be mediated by an H+ gradient-dependent transport system across the brush-border membrane of rats, rabbits and humans. The carrier-protein for this process is likely a dipeptide transport system.

Animals

[Initial ultrafiltration to the priming solution with preserved blood for cardiopulmonary bypass in infants].

In case of open heart surgery in infants, the initial priming solutions (IPS) of the cardiopulmonary bypasses (CPB) include considerable amount of preserved blood to assure us of the proper hematocrit during the CPB. Aiming at elimination of unfavorable effects of preserved blood on hearts and vessels, the ultrafiltrations (UF) to the IPS before the beginnings of CPB had been carried out in 42 pediatric cases. The IPS amounted to 915 +/- 25 (mean +/- SE) ml. in which 581 +/- 31 ml of preserved blood were included. The 1.5-fold amount infusions over the IPS, consisted of 5% glucose, normal saline and fresh frozen plasma, were added to the IPS, and just the same amount fluid were removed out by the UF. The concentrations of potassium, NH3, lactic acid and pyruvic acid in the IPS decreased significantly after UF (p = 0.001). The potassium concentrations were compared among the blood of patients (PB), the IPS before UF (IPS1), the IPS after UF (IPS2), and the mixed blood drawn 5-10 minutes after the beginnings of CPB (MB) in the cases under the age of 1 year (group-I, n = 26, 4.7 +/- 0.3 kg) and in the elders (group-E, n = 16, 15 +/- 2 kg). The results showed all significant differences but "IPS2 and MB" in group-I, and but "PB and MB" in group-E (ANOVA p = 0.001, p < 0.01 by Newman-Keuls). The 98% of cases kept their innate heart beatings until the aortic clamps at 22 +/- 1 degrees C (sending blood temp.).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Transfusion, Autologous

[Two cases of gross E-type tracheo-esophageal fistulae associated with interruption of the aortic arch and coarctation of the aorta in early infancy].

Two cases of Gross E-type tracheoesophageal fistulae associated with interruption of the aortic arch in one and coarctation of the aorta in the other in early infancy were treated radically at Nagano Children's Hospital during the preceding 4 months until January 1994. The tracheoesophageal fistulae were noticed after the first stage surgery for the aortic arch anomalies, because of the remarkable abdominal distension under the intubated and ventilated condition of general anesthesia. Both the bronchial and esophageal optical fiber examinations were performed which proved useful to detect the fistulae. In each case, the transcervical division of the fistula was performed on an emergency basis. The external diameter of the fistula was 4 and 5 mm respectively. The fistulae dilated synchronously with ventilation. The early detection and surgical correction of the tracheoesophageal fistula can prevent serious complications such as DIC as seen in the first case probably caused by respiratory infection associated with the prolonged mechanical ventilation. Successful intracardiac repair were performed in both cases on the 25th and 7th day following the correction of the fistulae respectively.

Aorta, Thoracic

[Reoperation for coarctation of the aorta and interrupted aortic arch].

This report presented four patients who underwent surgery for restenosis after repair of coarctation of the aorta (CoA) or interrupted aortic arch (IAA) at our institution between January 1980 and October 1994. Case #1 underwent primary repair for IAA, VSD, and PDA consisting of aortic arch reconstruction using a EPTFE (expanded polytetrafluoroethylene) graft of 10 mm in diameter at the age of four years. After 17 years, pressure gradient of 58 mmHg between the ascending aorta and the descending aorta prompted the reoperation. Case #2 underwent primary repair for CoA, VSD, and PDA consisting of a bypass between the ascending aorta and the descending aorta with an EPTFE graft of 11 mm in diameter at the age of three years. After 13 years, he had reoperation because of pressure gradient of 64 mmHg. Case #3 had pressure gradient of 20 mmHg between the upper and lower limb at the hospital discharge following patch angioplasty for CoA at five years of age. He underwent unsuccessful percutaneous transluminal balloon angioplasty at age 12 and had reoperation at age 15. Case #4 underwent subclavian flap angioplasty as the first stage operation for CoA, VSD, and PDA at 1 month after birth. About 9 months after the initial operation, the pressure gradient between the upper and lower limb had reached 40 to 50 mmHg, and the patient had reoperation at the age of 1 year. The reoperation method for cases #1, #2 and #3 consisted of bypass grafting from the left subclavian artery to the descending aorta under a simple cross clamping of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Measurement of tear electrolyte concentration and turnover rate using a flexible conductimetric sensor.

Tear fluid conductivity was measured by a non-invasive method. A flexible 3 mm-wide conductimetric sensor was placed inside the human subjects temporal lower cul-de-sac (similar to Schirmer test strip), and used to evaluate electrolyte concentration and turnover rate in tear for normal, healthy subjects aged between 30 to 85 years in a normal, light indoor environment. The tear electrolyte concentration was calculated from tear conductivity to give a mean value of 297 mEq/l (S.D. 30 mEq/l; n = 29) which was consistently with previously reported values. Tear turnover rate was calculated by a single exponential equation of tear conductivity change, following the application to the eye-drops of 40.0 milligrams sodium chloride solution. The mean turnover rate was 44.2% per minute (S.D. = 13.3% per minute; n = 30), being in agreement with previously reported values.

Adult

Antitumor effects of pirarubicin and epirubicin in combination with doxifluridine and cisplatin against mouse P388 leukemia.

In vivo antitumor activity of pirarubicin (THP) and epirubucin (EPI) in combination with doxifluridine (5'-DFUR) and cisplatin (CDDP) were examined using mouse P388 leukemia. THP (1.25-7.5 mg/kg) or EPI (1.25-15 mg/kg) was given intravenously on day 1, and then 5'-DFUR (125 or 250 mg/kg/day) and CDDP (4 mg/kg) were given orally on days 1-4 and intravenously on day 5 after tumor inoculation, respectively. Both THP and EPI enhanced the antitumor of a combination of 5'-DFUR and CDDP. The enhancement by THP was additive or synergistic, while that by EPI was additive. Cured animals were observed in the combination of THP with the two drugs, but not in that of EPI. Thus, in combination with 5'-DFUR and CDDP, THP was more effective against P388 leukemia than was EPI. The combination therapy using THP, 5'-DFUR and CDDP may be a novel chemotherapeutic approach to a variable type of tumors in clinical trials.

Animals

Calyculin A, a non-phorbol ester type tumor promotor, induced oxidative DNA damage in stimulated human neutrophil-like cells.

Calyculin A(CA) induced 8-hydroxydeoxyguanosine (8OHdG), typical of mutagenic oxidative DNA damage, in N-Formyl-Methionyl-Leucyl-Phenylalanine (FMLP)-stimulated dimethyl sulfoxide(DMSO)-differentiated HL60(DMSO-HL60), which has characteristics similar to those of human neutrophils. CA enhanced O2-generation in FMLP-stimulated DMSO-HL60. CA by itself neither induced 8OHdG nor O2-generation. FMLP by itself induced O2-generation, however, it did not induce 8OHdG. These findings suggest that CA exerts its tumor promotion activity through modulating O2-generation and through inducing oxidative DNA damage and that a common bioactive peptide induces oxidative DNA damage under a certain condition.

8-Hydroxy-2'-Deoxyguanosine

Structure and chromosomal mapping of genes for the mouse kappa-opioid receptor and an opioid receptor homologue (MOR-C).

Recent cDNA cloning studies have defined four members of the opioid receptor family, i.e., delta-, mu- and kappa-subtypes, and an opioid receptor homologue for unknown ligands. In this report, we isolated and analyzed mouse genomic DNA segments containing the kappa-opioid receptor gene and a gene for the opioid receptor homologue (designated as MOR-C). The genes are closely related each other in exon-intron organization, suggesting their evolutional relationship. Using in situ hybridization, we show that the kappa-opioid receptor gene and the MOR-C gene map to mouse chromosome 1A2-3 and 2H2-4, respectively.

Amino Acid Sequence

Changes in neuronal contribution to contractile responses of vas deferens of young and adult guinea pigs.

The response characteristics of vas deferens to electrical hypogastric nerve stimulation at various frequencies was studied in guinea pigs of 2 to 15 weeks old. In 2-week-old guinea pigs the stimulation induced monophasic contraction, some of which remained after blocking alpha 1-adrenoceptor and desensitizing P2-purinoceptors with prazosin and alpha, beta-methylene ATP, respectively. In guinea pigs of 10 to 15 weeks old stimulation induced biphasic contraction, which was almost completely inhibited by both blockers. These results suggest that some unknown component other than ATP and norepinephrine is involved in the transmission at 2 weeks, and that its relative significance changes during development.

Adenosine Triphosphate

Establishment of a human system that generates O2- and induces 8-hydroxydeoxyguanosine, typical of oxidative DNA damage, by a tumor promotor.

We have established a system in which a human cell line generated reactive oxygen species (ROS), using a dimethyl sulfoxide-differentiated promyelocytic leukemia cell line HL60 (DMSO-HL60), which has characteristics similar to those of human neutrophils. DMSO-HL60 generated O2- upon stimulation with a tumor promoter, phorbol myristate acetate (PMA). O2- generation, determined as O2- release from the PMA-stimulated cells by the reduction of cytochrome c, was dependent on the dose of PMA and reached almost maximal with 2.0 nM PMA. PMA dose-dependently increased 8-hydroxydeoxyguanosine (8OHdG) in DMSO-HL60, typical of mutagenic oxidative DNA damage. The 8OHdG level, determined by electrochemical detection with high performance liquid chromatography, also became almost maximal with 2.0 nM PMA. The amount of O2- generation and that of the 8OHdG induction by PMA in human neutrophils were similar to those in DMSO-HL60. Superoxide dismutase inhibited the 8OHdG induction by about 60%, whereas catalase, deferoxamine, or thiols inhibited it almost completely. Dilution of PMA-stimulated DMSO-HL60 decreased the concentration of ROS releasing to the media from the cells. However, it did not decrease the ROS generation per cell or the 8OHdG induction. The addition of H2O2 to unstimulated DMSO-HL60 did not increase the 8OHdG level. These findings indicate that DMSO-HL60 could be used as a substitute for human neutrophils, that the concentration of ROS is not the only determinant for the 8OHdG induction, but that it requires both acquisition of susceptibility to ROS by reduction of iron by O2- and formation of H2O2, and that ROS increase 8OHdG by attacking the ROS-generating cell.

8-Hydroxy-2'-Deoxyguanosine

Nutrient balance, metabolic response, and bone growth in VLBW infants fed fortified human milk.

The effects of fortification of preterm human milk were evaluated by comparing two groups of very low birth weight infants (birth weight < or = 1300 g, gestational age < or = 30 weeks): six fed preterm human milk fortified with a commercially available protein-mineral supplement (protein 0.7 g/dl, calcium 90 mg/dl, phosphorus 45 mg/dl) and seven fed unfortified preterm human milk. Nitrogen and energy balance studies were performed at an average age of 56 postnatal days. Nitrogen retention in the fortified group (348.2 +/- 70.5 mg/kg/day) was significantly greater than that in the unfortified group (196.0 +/- 50.0 mg/kg/day) and similar to that of fetuses of comparable gestational age. Energy stored by the two groups did not differ. At age 8 weeks, the infants in the fortified group had higher serum protein, higher serum albumin, and better mineral status (higher serum calcium and phosphorus and lower alkaline phosphatase and renal tubular reabsorption of phosphate). The bone density and width of the distal third radius, as measured by X-ray microdensitometry, were greater in the fortified group than in the unfortified group 12 weeks after birth. These results suggest that the supplement corrects any nutritional inadequacies of preterm human milk for very low birth weight infants.

Animals

Differences in relaxant effects of cyclic GMP on skinned muscle preparations from the proximal and distal colon of rats.

The relationship between the intracellular cyclic GMP content and relaxation of smooth muscle was studied in preparations from the proximal and distal colon of rats. Nitric oxide increased the cyclic GMP content of longitudinal muscle of both preparations to approximately the same extents. However, although nitric oxide at 0.03-10 microM induced concentration-dependent relaxation of the proximal segments, it did not induce any significant relaxation of the distal segments. The longitudinal muscle preparations were permeabilized by treatment with alpha-toxin to examine the relaxant effects of cyclic GMP on the contractile elements. Ca2+ induced contraction of the permeabilized muscle, the contraction consisting of a transient and subsequent tonic phases. Cyclic GMP (3-100 microM) reversed the tonic contractions induced by various Ca2+ concentrations (1-30 microM). The magnitude of the relaxant effect of cyclic GMP was significantly more in the proximal region than in the distal region. But in contrast to nitric oxide, cyclic GMP induced slight, but clear relaxation of the distal colon. The inhibitory effects of cyclic GMP on phasic contraction, like those on tonic contraction, were high in the proximal region and low in the distal region. These results suggest that the difference in the relaxant effects of nitric oxide in the proximal and distal longitudinal muscles is not due to a difference in extents of cyclic GMP generation, but mainly to a difference in the sensitivities of the contractile elements in the two regions to cyclic GMP.

Animals