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Biomedical subjects

S Takeuchi

Publications and source records attributed to S Takeuchi.

At least 199 records · Page 11Linked to original sources
PubMed1999

Downregulation of voltage-gated K(+) channels in rat heart with right ventricular hypertrophy.

The effects of myocardial hypertrophy on mRNA expression levels of voltage-gated K(+) channels were investigated using monocrotaline (MCT)-induced pulmonary hypertensive rats. The ratio of right ventricle weight to left ventricle plus septum weight on day 28 was increased significantly compared with control rats [control vs. MCT: 0.27 +/- 0.01 vs. 0.58 +/- 0.03 ms (n = 8-13); P < 0.05]. Electrocardiograms showed that QRS duration [control vs. MCT: 26.4 +/- 2.6 ms vs. 31.5 +/- 5.8 ms (n = 6); P < 0.05], Q-T interval [control vs. MCT: 100.8 +/- 8.9 ms vs. 110.0 +/- 4.2 ms (n = 6); P < 0.05] and corrected Q-T interval [Q-T(c); control vs. MCT: 8.4 +/- 0. 7 ms vs. 10.2 +/- 0.4 ms (n = 6); P < 0.05] were prolonged significantly on day 28. mRNA levels of Kv1.2, 1.5, 2.1, 4.2, and 4. 3 for day 28 assessed by ribonuclease protection assays were decreased significantly from control by 60 +/- 10, 76 +/- 3, 58 +/- 5, 81 +/- 5, and 45 +/- 12%, respectively (n = 3; P < 0.005), and Kv1.4 mRNA level for day 28 was unaffected [Kv1.4, control vs. MCT: 1.0 +/- 0.28 vs. 0.88 +/- 0.44 (arbitrary units) (n = 3); not significant (NS)]. On the other hand, there was no significant difference between control and MCT rats in mRNA levels of these Kv channels for day 14 [Kv1.2 (control vs. MCT): 1.0 +/- 0.25 vs. 0.87 +/- 0.18 (n = 3), NS; Kv1.4: 1.0 +/- 0.22 vs. 1.27 +/- 0.37 (n = 3), NS; Kv1.5: 1.0 +/- 0.16 vs. 0.91 +/- 0.28 (n = 3), NS; Kv2.1: 1.0 +/- 0.26 vs. 0.99 +/- 0.25 (n = 3), NS; Kv4.2: 1.0 +/- 0.15 vs. 1.22 +/- 0.28 (n = 3), NS; Kv4.3: 1.0 +/- 0.20 vs. 1.21 +/- 0.28 (n = 3), NS]. These findings suggest that altered ventricular repolarization at the advanced stage of hypertrophy may be the result of an inhibition of gene expression of multiple types of voltage-gated K(+) channels.

Animals↗
PubMed1999

Ovarian cancer: loss of heterozygosity frequently occurs in the ATM gene, but structural alterations do not occur in this gene.

Ataxia-telangiectasia is a multisystem recessive disease characterized clinically by cerebellar ataxia, oculocutaneous telangiectasias, immunodeficiency, sensitivity to radiomimetic agents and an increased predisposition to cancer. This pleiotropic disorder is caused by mutations in the ATM gene, which is located at the human chromosomal region 11q23. Loss of heterozygosity (LOH) at 11q22-q23 is a frequent event in ovarian cancer, suggesting the presence of a tumor suppressor gene in this region. We have found that LOH in the ATM gene occurred in 44% of informative cases in a series of 22 primary ovarian tumors. LOH of this region occurred at the same frequency during the advanced stages (III-IV; 3/9, 33%) as in the early stages (I-II; 4/13, 31%) of ovarian cancer. To investigate the role of ATM in ovarian cancer, we used a PCR-based single-strand conformation polymorphism assay for mutation detection of the entire coding sequence of the ATM gene (65 exons) in 22 ovarian tumors. No somatic alterations of the ATM gene were found in these ovarian cancer samples including those with LOH present in the ATM gene. Our study has identified a region (11q23) which probably contains a frequently altered tumor suppressor gene in ovarian cancer, and this gene does not appear to involve the coding sequences of the ATM gene.

Adenocarcinoma↗
PubMed1999

Effects of green tea tannin on cisplatin-induced nephropathy in LLC-PK1 cells and rats.

A study was conducted to clarify whether green tea tannin ameliorated cisplatin-induced renal injury in terms of lactate dehydrogenase and malondialdehyde leakage from a renal epithelial cell line, swine-derived LLC-PK1 cells in culture. Green tea tannin was shown to suppress the cytotoxicity of cisplatin, the suppressive effect increasing with the dose of green tea tannin. The effect of cisplatin was then investigated in rats given green tea tannin for 40 days before cisplatin administration and in control rats given no green tea tannin. In control rats, blood, urinary and renal parameters and the activities of antioxidative enzymes in renal tissue deviated from the normal range, indicating dysfunction of the kidneys. In contrast, rats given green tea tannin showed decreased blood levels of urea nitrogen and creatinine, and decreased urinary levels of protein and glucose, reflecting less damage to the kidney. In this group, the activity of catalase in the renal tissue was increased, while the level of malondialdehyde was decreased, suggesting the involvement of radicals in the normalizing of kidney function. Based on the evidence available it appeared that green tea tannin eliminated oxidative stress and was beneficial to renal function.

Animals↗
PubMed1999

Strategy for balancing anticoagulation and hemostasis in aortocoronary bypass surgery: blood conservation and graft patency.

The minimal effective dose of aprotinin on hemostasis under normothermic perfusion, the influence of anticoagulant therapy on graft patency, and the thromboembolic and hemorrhagic events were investigated after aortocoronary bypass graft operation (CABG). One hundred CABG patients under normothermic perfusion were randomly divided into the following groups: (1) coumadin plus acetylsalicylic acid (ASA) (n=32); no aprotinin used during cardiopulmonary bypass (CPB); (2) minimal-dose, 10(6) KIU during CPB, aprotinin used, followed by ASA and coumadin (n=36); and (3) very low-dose, total of 2x10(6) KIU before CPB and during CPB; aprotinin used; anticoagulation therapy with heparin early after surgery and followed by replacement with ASA and coumadin (n=32). The patency of arterial grafts was 100% in all groups. The patency of vein grafts was 95-98% and there was no difference among the groups. The blood loss was significantly reduced in both aprotinin groups (groups 2 and 3) compared to the coumadin plus ASA group, although no difference existed between the 2 aprotinin groups. Postoperative thrombotic and hemorrhagic events were not observed in any group. From this study, it was concluded that 10(6) KIU aprotinin in pump-prime-only followed by oral ASA and coumadin was the recommendation from the benefit/cost consideration.

Adult↗
PubMed1999

[Antiretroviral agent nevirapine: its pharmacological action and potential for clinical use].

Nevirapine (NVP) is a potent noncompetitive inhibitor of the reverse transcriptase enzyme, which is necessary for HIV replication. NVP selectively inhibits HIV-1 but not HIV-2 and any of the human DNA polymerases. NVP is active against ZDV-resistant HIV-1 and synergistic with nonnucleoside reverse transcriptase inhibitors. NVP has a favorable pharmacokinetic profile, becomes widely distributed throughout body tissues including the central nervous system, and is active in the adult at an oral dose of 200 mg administered twice daily after a 2 week lead-in dose of 200 mg/day due to its long elimination half life. Although the currently used protease inhibitors (PIs) may undergo more rapid rates of metabolism because NVP induces CYP3A, No dosage adjustments are required when NVP is taken in combination with PIs so far. When administered in triple combinations with antiretroviral agents, the antiviral effect of NVP has been profound and sustained in HIV-infected patients, particularly in naive patients to antiretroviral therapy. Resistance to NVP is rapid when given as monotherapy, but this is altered and made less clinically relevant when NVP is administered as a triple combination. NVP has a safety profile that does not overlap with other antiretroviral therapies, the most common treatment-limiting reaction being rash. It seems that NVP would be a very useful option in combination with antiretroviral agents.

Adult↗
PubMed1999

Skull metastasis of Ewing's sarcoma--three case reports.

Three cases of skull metastasis of Ewing's sarcoma were treated. The metastatic lesion was located at the midline of the skull above the superior sagittal sinus in all cases. Surgery was performed in two patients with solitary skull lesions involving short segments of the superior sagittal sinus without remarkable systemic metastasis, resulting in good outcome. The third patient had extensive, multiple tumors involving the superior sagittal sinus which could not be excised, and died due to intracranial hypertension. The surgical indication for skull metastasis of Ewing's sarcoma depends on the location and length of the involved superior sagittal sinus, and general condition.

Adolescent↗
PubMed1999

Neuronal damage in gerbils caused by intermittent forebrain ischemia.

OBJECT: The purpose of this study was to investigate the possibility of preventing cumulative neuronal damage after repetitive severe ischemia. METHODS: The authors monitored ischemic depolarization in the gerbil hippocampus, which has recently been shown to be a good experimental model of the effects of brief ischemia on the brain, and evaluated neuronal damage in the CA1 subregion 7 days after the ischemic insult. In a single-ischemia paradigm, the results indicate that induction of ischemia-induced neuronal damage depended on the duration of ischemic depolarization. Neuronal damage can be detected in the CA1 subregion after a period of depolarization lasting 210 seconds. Using a double-ischemia paradigm in which the animals were subjected to two periods of ischemia, there was apparently no accumulation of neuronal damage from the first ischemic episode to the second, provided the duration of the first period of ischemic depolarization did not exceed 90 seconds. Neuronal damage accumulated when the duration of the first ischemia episode exceeded 90 seconds, regardless of the duration of the reperfusion interval between the two ischemic insults. Finally, when the ischemic insult was spread over four separate episodes, each lasting 90 seconds (with a reperfusion interval of 5 minutes), neuronal damage was not found when the total depolarization period was less than 420 seconds. CONCLUSIONS: The authors conclude that cumulative neuronal damage may be avoided by adopting an intermittent ischemia approach. The implications of these results for human surgery requiring temporary occlusion of the cerebral arteries are discussed.

Action Potentials↗
PubMed1999

Radiologic and histopathologic evaluation of canine artery occlusion after collagen-coated platinum microcoil delivery.

BACKGROUND AND PURPOSE: Platinum coil embolization is one of the significant advances in interventional neuroradiologic techniques that has been introduced this decade. Our purpose was to evaluate the angiographic and histologic effects of collagen-coated platinum microcoil delivery in the canine artery. METHODS: We embolized the bilateral internal maxillary arteries of 18 dogs; one uncoated and one collagen-primed coil was used in each dog. We evaluated all coils by angiography, macroscopy, and scanning electron microscopy within 30 minutes of embolization. We then studied a proportional number of coated and collagen-primed coils at either 1 or 3 days, or 1, 2, 3, 4, 8, 12, or 16 weeks postoperatively. RESULTS: Six (33%) of 18 arteries embolized with uncoated coils were occluded 30 minutes after delivery, whereas 11 (61%) of 18 arteries treated with collagen-primed coils were occluded within 30 minutes of embolization. Late occlusion (3 weeks after embolization) occurred in 2 (25%) of 8 arteries embolized with untreated coils, and 6 (75%) of 8 arteries embolized with collagen-primed coils. We calculated differences in late occlusion rates by the chi2 (chi-square) test, and found these differences were significant (P=.04). Histologic findings of arteries embolized with unprimed coils revealed endothelial cell growth was limited to the organized thrombi 4 weeks after coil delivery. In contrast, endothelial cells grew directly on the collagen-primed coils 3 days postoperatively, and coils were completely covered by endothelial cells within 2 weeks. We found an organized thrombus in the inner space of coils in angiographically occluded arteries, a finding that was not evident in angiographically patent arteries. CONCLUSION: Collagen-coated platinum coils can produce rapid and stable occlusion of embolized vessels.

Angiography↗
PubMed1999

Embolization of cerebral arteriovenous malformations achieved with polyvinyl alcohol particles: angiographic reappearance and complications.

BACKGROUND AND PURPOSE: The appropriate choice of embolic materials with respect to the permanency of obliterated nidi after embolization and complications related to the procedure is essential for safe and effective embolization of cerebral arteriovenous malformations (AVMs). Our purpose was to ascertain the recanalization and complication rates after AVM treatment with polyvinyl alcohol (PVA) particles. METHODS: Between 1988 and 1994, 36 AVMs were embolized with PVA particles at our institution. Follow-up angiographic findings and occurrence of complications during the embolization procedures were analyzed retrospectively. RESULTS: Complete obliteration of the nidus immediately after embolization was achieved in five patients, and 80% to 99% obliteration was attained in 12 patients. Fifty-one follow-up angiographic examinations were performed 1 week to 60 months (mean, 7 months) after embolization in 31 patients. An increase in nidal size was seen on 15 follow-up angiograms (29%) and a decrease was seen in seven (14%). In 28 of the 51 angiograms obtained more than 1 month after follow up (mean, 13 months), 12 (43%) showed AVM enlargement. In four (80%) of five cases of complete obliteration, nidi reappeared on follow-up angiograms. Hemorrhagic complications occurred in three cases and ischemic ones in seven. One patient (3%) died and five (14%) suffered persistent neurologic deficits. CONCLUSION: Embolization with PVA particles can produce significant volume reduction in AVM nidal size, but recanalization is a distinct possibility.

Adolescent↗
PubMed1999

Real time measurement of heparin concentration during cardiopulmonary bypass.

BACKGROUND: A heparin/protamine titration system for measurement of heparin levels (Hepcon) is promising for efficient anticoagulation during cardiopulmonary bypass (CPB). METHODS: Fifty-seven patients subjected to CPB were divided into two groups, control (n = 24) and Hepcon groups (n = 33). The Hepcon group was further divided into three subgroups according to perfusion temperature. For the control group, conventional administration of an anticoagulant (300 IU/kg of heparin) and reversal protocol (heparin 1: protamine 1) was performed. For the Hepcon group, a heparin dose-response assay directed the initial dose of heparin. Hepcon also determined the dose of protamine by the titration. The initial dose of heparin in the control group (300 IU/kg) was statistically less than that of Hepcon group (360+/-80 IU/kg). RESULTS: In the Hepcon group, the sensitivity to heparin was correlated with coagulation time (r = -0.78) and antithrombin III levels (r = 0.70), and individual difference of sensitivity resulted in a wide range of dosage (160 to 490 IU/kg). A strong correlation was observed between plasma and whole blood concentration of heparin (r = 0.86). However, they did not correlate with ACT values. Perfusion temperature didn't affect the heparin level, but did the ACT value. In the Hepcon group, the dose of protamine was significantly less and adverse events were rare. CONCLUSIONS: In conclusion, whole blood heparin measurements correlated well with plasma heparin concentration. Protamine titration of heparin reduced the dose of protamine and decreased the chance of adverse reactions.

Anticoagulants↗
PubMed1999

GnRH agonist. Increasing the pregnancy rate after combined treatment with hMG/hCG and direct intraperitoneal insemination.

OBJECTIVE: To evaluate the efficacy of the GnRH agonist (GnRHa) administered in conjunction with human menopausal gonadotropin/human chorionic gonadotropin hMG/hCG and direct intraperitoneal insemination (DIPI) in women with long-standing unexplained infertility. STUDY DESIGN: A prospective, randomized, non-blind analysis. During the period May 1995-December 1996, couples with unexplained infertility who failed to conceive following superovulation combined with IUI for at least seven cycles were prospectively enrolled and followed. Pregnancy rates per cycle and per patient of DIPI were compared between groups of hMG/hCG with (GnRHa[+] controlled ovarian hyperstimulation [COH] group) or without (GnRHa[-] COH group) GnRHa. RESULTS: Thirty-four women (59 cycles) underwent COH with hMG and GnRHa, and 31 women (49 cycles) received hyperstimulation with hMG alone. The pregnancy rates for the women administered GnRHa significantly exceeded those of the patients who did not receive GnRHa both per treatment cycle (35.6% versus 14.3%) and per couple (55.9% versus 22.5%). CONCLUSION: The use of GnRHa with hMG/hCG and DIPI treatment significantly increased the pregnancy rate in women with long-standing infertility.

Adult↗
PubMed1998

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult↗
PubMed1998

Polar amino acid-rich sequences bind to polyglutamine tracts.

Polyglutamine tracts are found in different proteins including transcription factors and cofactors as well as in triplet repeat disease gene products. To characterize the protein motif that binds to the polyglutamine tract, we screened a human embryonic brain cDNA library with the polyglutamine tract of Brn-2 as bait using the yeast two-hybrid method. All six isolated clones encoding polyglutamine tract binding proteins were rich in polar amino acids. Three of these clones could form polar helical structures. These observations suggest that polar amino acid-rich sequences are essential for binding to the polyglutamine tract.

Amino Acid Sequence↗
PubMed1998

Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair.

To analyze the function of the xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair, we examined repair of UV-induced cyclobutane pyrimidine dimer (CPD) in transcribed and non-transcribed strands of the dihydrofolate reductase gene of xeroderma pigmentosum group A (XP-A) cell line (XP12ROSV) which was transfected with various types of mutant XPA cDNA. The transfectant overexpressing mutant XPA with a defect in the interaction with either ERCC1, replication protein A (RPA), or general transcription factor TFIIH, showed more or less decreased repair of CPD in each strand in parallel, while in the transfectant overexpressing R207G (Arg207to Gly) mutant XPA derived from XP129, a UV-resistant XP12ROSV revertant, the rate of CPD repair was almost normal in each strand. We also examined the dose responses of the XPA protein on CPD repair in each strand by the modulation of the expression levels of wild-type or R207G mutant XPA using an inducible expression system, LacSwitchtrade mark promoter. There were good correlations between the rate of CPD repair in each strand and the amount of XPA protein produced in these Lac cells. Our results indicate that the XPA protein is equally important for the CPD repair in both transcribed and non-transcribed strands and that the R207G mutation found in XP129 may not be responsible for a selective defect in CPD repair in the non-transcribed strand in XP129.

Cell Line↗
PubMed1998

Frequent loss of heterozygosity on the long arm of chromosome 6: identification of two distinct regions of deletion in childhood acute lymphoblastic leukemia.

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identified nonrandom chromosomal abnormalities of the long arm of chromosome 6. Most of the alterations are deletions that are thought to be indicative of the presence of a tumor suppressor gene that is mutated on the remaining allele. These observations led us to consider whether 6q loss may contribute to the pathogenesis of childhood ALL. To define further a region containing this gene, we analyzed the loss of heterozygosity (LOH) of chromosome 6 in 113 primary ALL samples with matched normal DNA using 34 highly informative microsatellite markers. LOH was found in 17 (15%) samples at one or more of the loci, and partial or interstitial deletions of 6q were detected in 11 of these tumors. On the basis of these results, we performed a detailed deletional map and identified two distinct regions of deletion. The first region is flanked by D6S283 and D6S302 loci at 6q21-22. The second region is flanked by D6S275 and D6S283 loci at 6q21. Clinical analysis determined that LOH of 6q was demonstrated both in precursor-B cell ALLs (15 of 93; 16%) and in T cell ALLs (2 of 19; 11%). In addition, 19 patients have been studied at diagnosis and relapse; 18 showed the same 6q21-22 structural abnormality at relapse (normal, 16 patients; LOH, 2 patients) as their initial presentation, suggesting, albeit with a small patient sample size, that 6q21-22 deletions may be an initial event in leukemogenesis and may occur less frequently during the progression of childhood ALL. These data suggest the presence of putative tumor suppressor genes on chromosome arm 6q that are important in the development of both T and precursor-B childhood ALLs. Our map provides important information toward cloning putative ALL tumor suppressor genes.

Child↗
PubMed1998

Molecular cloning of the chicken melanocortin 2 (ACTH)-receptor gene.

The chicken melanocortin 2-receptor (MC2-R) gene was isolated. It is found to be a single copy gene encoding a 357 amino acid protein, sharing 65.8-68.7% identity with mammalian counterparts. The chicken MC2-R mRNA is expressed in the adrenal and spleen, suggesting that the receptor mediates both endocrine and immunoregulatory functions of ACTH in the chicken. The amino acid sequence of the chicken MC2-R is collinear with those of other subtypes of MC-R, whereas all cloned mammalian MC2-Rs contain a gap in the third intracellular loop, suggesting that mammalian MC2-R molecules have evolved by lacking a part of the domain which determines the specificity of signal transduction in G-protein coupled receptors. Interestingly, the codon usage differs dramatically between MC1-R and MC2-R in the chicken; the GC-contents at the third codon position in MC1-R and MC2-R are 94.6 and 50.6%, respectively. It may reflect selective constraints on the usage of synonymous codons.

Adrenal Glands↗
PubMed1998

Inwardly rectifying K+ currents in intermediate cells in the cochlea of gerbils: a possible contribution to the endocochlear potential.

The stria vascularis in the cochlea generates the endocochlear potential (EP) and secretes K+-rich endolymph; both are indispensable for normal sound transduction by hair cells. K+ conductance in the intermediate cell, one of the several types of cells constituting the stria vascularis, was investigated by the whole-cell patch-clamp technique. Inwardly-rectifying K+ (Kir) currents were the major currents observed. The currents were inhibited dose-dependently by Ba2+, quinine, verapamil and Cs+, but not by tetraethylammonium (20 mM), 4-aminopyridine (5 mM) or Cd2+ (1 mM). The similarity between the effect of inhibitors on Kir currents and on the EP (Takeuchi et al., Hearing Res., 101 (1996) 181-185) suggests a direct contribution of the Kir conductance to the generation of the EP.

4-Aminopyridine↗