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Biomedical subjects

T Takagi

Publications and source records attributed to T Takagi.

At least 181 records · Page 10Linked to original sources

Deterioration of ocular motor dysfunction after transvenous embolization of dural arteriovenous fistula involving the cavernous sinus.

We treated 9 patients with the dural arteriovenous fistula involving the cavernous sinus by transvenous embolization. Two patients experienced deterioration of oculo-motor dysfunction after transvenous embolization. We can speculate about two different kind of causes by which patients symptoms deteriorated according to the result of intrasinus pressure recorded during the embolization [1]: high intrasinus pressure caused by the obliteration of the drainage pathway resulted in cranial nerve palsy in one case [2]; implanted coils directly compressed the cranial nerve in another case. Fortunately our cases recovered, but some kind of preventative measures may be needed in similar cases.

Arteriovenous Fistula↗

Effects of 4-hydroperoxy ifosfamide in combination with other anticancer agents on human cancer cell lines.

Ifosfamide is one of the currently available anticancer agents with a broad spectrum of clinical activity against a variety of tumors. To investigate its optimal combinations, we studied the effect of 4-hydroperoxy ifosfamide (the active form of ifosfamide) in combination with other anticancer agents against two human cancer cell lines, MG-63 (an osteosarcoma cell line) and MOLT-3 cells (a T-cell leukemia cell line). The cells were incubated for 4 days and 3 days, respectively, in the presence of 4-hydroperoxy ifosfamide and the other agent. Cell growth inhibition was determined by MTT assay. The effects of these drug combinations at the concentration producing 50% inhibition (IC50) were analyzed by the isobologram method. 4-Hydroperoxy ifosfamide showed additive effects with bleomycin, cisplatin, cytarabine, doxorubicin, etoposide, 5-fluorouracil, and mitomycin C, while it showed a protective effect with methotrexate in both cell lines. 4-Hydroperoxy ifosfamide showed an additive effect with vincristine in the MG-63 cell line, while it showed a sub-additive effect in the MOLT-3 cell line. No anticancer agents tested showed a supra-additive effect with 4-hydroperoxy ifosfamide. These data suggest that ifosfamide is advantageous for simultaneous administration with a majority of the anticancer agents we studied. Methotrexate is an inappropriate drug for simultaneous administration with ifosfamide.

Antineoplastic Agents, Alkylating↗

Noninvasive evaluation of pulmonary capillary wedge pressure in patients with acute myocardial infarction by deceleration time of pulmonary venous flow velocity in diastole.

OBJECTIVES: This study investigates the correlation between deceleration time of diastolic pulmonary venous flow (PV-DT) and of early filling mitral flow (LV-DT), and pulmonary capillary wedge pressure (PCWP) in patients with acute myocardial infarction (AMI). BACKGROUND: An earlier study suggests that Doppler-derived LV-DT provides an accurate means of estimating PCWP in postinfarction patients with left ventricular systolic dysfunction. Furthermore, recent studies have suggested that PCWP correlates better with PV-DT than with LV-DT. However, the value of PV-DT and LV-DT for assessment of PCWP in patients with AMI has not been evaluated. METHODS: In 141 consecutive patients with AMI, we measured PV-DT and LV-DT by Doppler echocardiography, and compared these variables with PCWP measured using a Swan-Ganz catheter. RESULTS: There was a weak negative correlation between the LV-DT and PCWP (r = -0.54). Although the sensitivity of < or =130 ms in LV-DT in predicting > or =18 mm Hg in PCWP was high (86%), its specificity was low (59%). On the other hand, a very close negative correlation was found between PV-DT and PCWP (r = -0.89). The sensitivity and specificity of < or =160 ms in PV-DT in predicting > or =18 mm Hg in PCWP were 97% and 96%, respectively. CONCLUSIONS: In patients with AMI, Doppler-derived PV-DT showed a stronger correlation with PCWP than LV-DT.

Adult↗

Characterization of plasmid DNA binding and uptake by peritoneal macrophages from class A scavenger receptor knockout mice.

PURPOSE: Plasmid DNA (pDNA) has become an important class of macromolecular agent suitable for non-viral gene therapy as well as DNA vaccination. Our recent study has suggested that pDNA is taken up by mouse peritoneal macrophages via a specific mechanism mediated by a receptor similar to the scavenger receptor (SR). This study was designed to further characterize the pDNA uptake by macrophages in order to elucidate the mechanism. METHODS: The binding and uptake of pDNA labeled with 32P or a fluorescent marker were studied in vitro using cultured Chinese hamster ovary (CHO) cells expressing the class A scavenger receptor (SRA) and peritoneal macrophages from SRA-knockout mice. RESULTS: pDNA binding and uptake by CHO(SRA) cells were minimal and almost identical to that by wild-type CHO cells. Macrophages from the knockout mice showed pronounced pDNA binding and uptake as did the control macrophages. In both types of macrophage, pDNA binding was significantly inhibited by cold pDNA, polyinosinic acid and dextran sulfate but not by polycytidylic acid or Ac-LDL. These results provide direct evidence that SRA is not responsible for the significant binding and subsequent uptake of pDNA by mouse peritoneal macrophages. Further binding experiments revealed that, in addition to polyinosinic acid and dextran sulfate, heparin was a potent inhibitor among a variety of polyanionic compounds such as polynucleotides, anionic polysaccharides and modified proteins including Ox-LDL. CONCLUSIONS: The present study suggest that pDNA binding and uptake by mouse peritoneal macrophages are mediated by a specific mechanism to some defined polyanions not by scavenger receptors. The finding would be an important basis for further studies to elucidate the mechanism(s) of pDNA uptake by macrophages.

Animals↗

A radiation hybrid map of the rat genome containing 5,255 markers.

A whole-genome radiation hybrid (RH) panel was used to construct a high-resolution map of the rat genome based on microsatellite and gene markers. These include 3,019 new microsatellite markers described here for the first time and 1,714 microsatellite markers with known genetic locations, allowing comparison and integration of maps from different sources. A robust RH framework map containing 1,030 positions ordered with odds of at least 1,000:1 has been defined as a tool for mapping these markers, and for future RH mapping in the rat. More than 500 genes which have been mapped in mouse and/or human were localized with respect to the rat RH framework, allowing the construction of detailed rat-mouse and rat-human comparative maps and illustrating the power of the RH approach for comparative mapping.

Animals↗

A novel presenilin-2 splice variant in human Alzheimer's disease brain tissue.

Mutations in the presenilin-1 (PS-1) and presenilin-2 (PS-2) genes account for the majority of cases of early-onset familial Alzheimer's disease (AD). Alternative splicing forms of the PS-1 and PS-2 gene products have previously been reported in fibroblast and brain tissue from both familial and sporadic AD patients, as well as from normal tissues and cell lines. We demonstrate here unusual alternative splicing of the PS-2 gene that leads to the generation of mRNA lacking exon 5 in human brain tissue. This product was more frequently detected in brain tissue from sporadic AD patients (70.0%; 21 of 30) than from normal age-matched controls (17.6%; three of 17). In cultured neuroblastoma cells, this splice variant was generated in hypoxia but not under other forms of cellular stress. Hypoxia-mediated induction of this splice variant was blocked by pretreatment of neuroblastoma cells with the protein synthesis inhibitor cycloheximide or antioxidants such as N-acetylcysteine and diphenyl iodonium, suggesting that hypoxia-mediated oxidant stress might, at least in part, underlie the alternative splicing of PS-2 mRNA through de novo protein synthesis. Furthermore, the stable transfectants of this splice variant produced the N-terminal part of PS-2 protein (15 kDa) and were more susceptible to cellular stresses than control transfectants. These results suggest the possibility that altered presenilin gene products in stress conditions may also participate in the pathogenesis of AD.

Aged↗

Paroxysmal kinesigenic choreoathetosis locus maps to chromosome 16p11.2-q12.1.

Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.

Adolescent↗

Adrenomedullin and atrial natriuretic peptide concentrations in normal pregnancy and pre-eclampsia.

Adrenomedullin (AM) is a peptide that elicits a long-lasting vasorelaxant activity, while atrial natriuretic peptide (ANP) has also been shown to be a potent vasodilatory agent. To clarify the possible role of AM and ANP in the physiology of pregnancy and pathophysiology of pre-eclampsia, we measured plasma concentrations of these peptides in non-pregnant women, normal pregnant women and women with pre-eclampsia. A gradual increase in plasma AM was observed as pregnancy progressed. The plasma AM concentrations during the second trimester (12.7 +/- 1.4 fmol/ml) were significantly elevated, in comparison with the non-pregnant follicular phase (6.4 +/- 0.61 fmol/ml), luteal phase (6.0 +/- 0.49 fmol/ml), and the first trimester (6.5 +/- 0.8 fmol/ml). The plasma AM concentrations of the third trimester (21.5 +/- 1.4 fmol/ml) were significantly elevated when compared with those of the second trimester (P < 0.05). Northern blot analysis confirmed the expression of the AM mRNA transcript (1.6 kb) in third trimester placentas. In comparison with those observed at term (25.3 +/- 4.5 fmol/ml), the plasma concentrations were significantly reduced post-partum (6.4 +/- 0.6 fmol/ml). In the third trimester, plasma AM concentrations did not differ significantly between women with pre-eclampsia (17.2 +/- 2.3 fmol/ml) and normal pregnant women. In contrast, the plasma ANP concentrations in pre-eclampsia (39.5 +/- 7. 1 pg/ml) were significantly elevated when compared with those of the normal third trimester (14.4 +/- 1.4 pg/ml) (P < 0.05). ANP concentrations were reasonably constant throughout the pregnancy.

Adrenomedullin↗

Genomic structure of the amphioxus calcium vector protein.

Calcium vector protein (CaVP) is an EF-hand Ca(2+)-binding protein, which is unique to the protochordate, amphioxus. CaVP is supposed to act as a Ca(2+) signal transductor, but its exact function remains unknown. Not only its function but also its exact evolutionary relationship to other Ca(2+)-binding proteins is unclear. To investigate the evolution of CaVP, we have determined the complete sequences of CaVP cDNAs from two amphioxus species, Branchiostoma lanceolatum and B. floridae, whose open reading frame cDNA and amino acid sequences show 96.5 and 98.2% identity, respectively. We have also elucidated the structure of the gene of B. floridae CaVP, which is made up of seven exons and six introns. The positions of four of the six introns (introns 1, 2, 3, and 5) are identical with those of calmodulin, troponin C, and the Spec protein of the sea urchin. These latter proteins belong to the so-called troponin C superfamily (TnC superfamily) and thus CaVP likely also belongs to this family. Intron 6 is positioned in the 3' noncoding region and is unique to CaVP, so it may represent a landmark of the CaVP lineage only. The position of intron 4 is not conserved in the genes of the TnC superfamily or CaVP, and seems to result from either intron sliding or the addition of an intron (randomly inserted into or close to domain III) to the genes of the TnC superfamily during their evolution.

Amino Acid Sequence↗

Osteoplastic anterolateral vertebrotomy without fusion for multilevel cervical ossification of the posterior longitudinal ligament.

OBJECTIVE: To introduce a new method for osteoplastic anterolateral vertebrotomy without fusion to resect multilevel cervical ossification of the posterior longitudinal ligament. METHODS: A multilevel vertebral column graft containing portions of the intervertebral discs is cut with a microsurgical saw from the anterolateral part of the vertebra via a thin lateral gutter placed in advance. A sufficiently wide oblique operative field is provided for resection of the ossified ligament with this method, and only a narrow bony defect remains after simple replacement of the vertebral graft. Postoperatively, patients are allowed to walk, usually within 2 to 3 days, wearing simple cervical collars. RESULTS: Twelve patients underwent resection of the ossified ligaments in two to five vertebral bodies. Clinical results were satisfactory except in one patient, who died as a result of a pulmonary embolism that occurred 10 days after surgery. In all of the other patients, the vertebral column grafts were fused within a few months, and there were no graft-related problems. Postoperative lateral radiographs revealed that cervical alignment was preserved, with intervertebral mobility at the operated segment in flexion-extension views. CONCLUSION: The osteoplastic anterolateral vertebrotomy method provided a sufficiently wide operative field for satisfactory resection of multilevel cervical ossification of the posterior longitudinal ligament, simplifying graft replacement and postoperative patient care. The cervical alignment was preserved.

Adult↗

Clustering and detection of 5' splice sites of mRNA by k weight-matrices model.

We propose a novel method to detect 5' splice sites of eukaryotic mRNA. We have grouped the 5' splice splice sites into various classes. The clustered sites are represented by a set of PWMs. The clustering algorithm is similar to k-means clustering algorithm but the distance definition and the training score function were arranged. The clustered PWMs were applied to 5' splice site detection. The results showed an improvement in comparison with traditional single PWM. The result of the clusters suggests there are new motifs of 5' splice sites.

Algorithms↗

Time and memory efficient algorithm for extracting palindromic and repetitive subsequences in nucleic acid sequences.

Genomic science and structural biology meet in the relationship between the sequence and the structure of nucleic acids. The structure that supports each function is preserved in the process of evolution as specific sequences. Particularly, the same sequence which appears in a different place such as a palindromic or repetitive sequence has biophysical meaning: recognition site of dimers, forming stem-loops, and contributions to global structure of nucleic acids. Also, the genetic network, transduction pathway, and tissue specificity largely depend on these. Although the relationship between them can be found experimentally, there is increasing demand for automated analysis. Especially, it is desirable to extract the same character sequences of arbitrary length (especially, very long ones) which co-occur at an arbitrary separation. We propose an algorithm to identify the maximum match sequence at each position with a calculation cost of O(N log N) and memory space of O(N). Applying it to some sequences, we found unexpectedly large palindromes and repeats in DNA.

Algorithms↗

Nocardia asteroides pneumonia, subcutaneous abscess and meningitis in a patient with advanced malignant lymphoma: successful treatment based on in vitro antimicrobial susceptibility.

Nocardia asteroides pneumonia, subcutaneous abscess and meningitis without brain abscesses developed in a patient with advanced non-Hodgkin's lymphoma, who had received corticosteroid therapy and cancer chemotherapy for a long time. At the time of nocardial pneumonia, profound lymphocytopenia and hypogammaglobulinemia was seen. The severely immunosuppressed condition most likely accounted for the uncommon infection, nocardiosis. The organism isolated from the sputum, subcutaneous abscess and cerebrospinal fluid was strongly resistant to cotrimoxazole, which is the recommended standard treatment, but it was susceptible to imipenem (IPM) and erythromycin (EM) in an in vitro antimicrobial susceptibility study. The patient's nocardiosis responded well to chemotherapy including IPM and EM.

Abscess↗

[Evaluation of mitral valve lesions in patients with infective endocarditis by three-dimensional echocardiography].

Recognition of the involved lesions is extremely important in mitral valve repair for infective endocarditis. Transesophageal echocardiography (TEE) is more sensitive for the detection of lesions than transthoracic echocardiography, but localization of the lesions is sometimes difficult by TEE. Three-dimensional (3D) TEE provides images of the mitral valve similar to the view from the left atrium. This study evaluated the value of 3D echocardiography for the diagnosis of involved lesions in 12 patients who underwent surgery for mitral regurgitation due to infective endocarditis. The location of the lesion in the mitral valve was classified as the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet, respectively. In all patients, the involved sites were confirmed at operation. The sensitivities of 3D TEE for detecting the lesions at the medial, central and lateral portions of the anterior leaflet, and the medial, middle and lateral scallops of the posterior leaflet were 100%, 78% and 67%, and 100%, 100% and 100%, respectively. The specificities were 90%, 100% and 78%, and 100%, 100% and 100%, respectively. The lesions diagnosed by 3D TEE coincided with lesions confirmed at operation in 23 (92%) of 25 lesions. 3D TEE is useful for the assessment of the involved lesion of the mitral valve in patients with infective endocarditis.

Echocardiography, Three-Dimensional↗

[Usefulness of tissue harmonic imaging for the detection of left ventricular endocardial border].

Assessment of segmental wall motion is one of the most challenging tasks in echocardiography. One major limitation is impairment of echocardiographic regional wall motion by incomplete endocardial definition. The newly developed tissue harmonic imaging method may improve the detection of left ventricular endocardial border. This study examined the impact of native tissue harmonic imaging on endocardial border definition. Fundamental and harmonic imaging were compared for detecting the endocardial border in 96 segments of 16 patients (age 54 +/- 8 years). Visualization of endocardial border was better with harmonic imaging than with fundamental mode in 49% (47 of 96 segments). Thus, tissue harmonic imaging has a significant impact on endocardial border definition.

Cardiomyopathies↗