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Biomedical subjects

T Takagi

Publications and source records attributed to T Takagi.

At least 289 records · Page 16Linked to original sources

In vitro effects of sho-saiko-to on production of granulocyte colony-stimulating factor by mononuclear cells from patients with chronic hepatitis C.

During the past 2 years, drug-induced interstitial pneumonia was reported in 66 Japanese patients, mainly among chronic hepatitis C patients, undergoing treatment with the Japanese herbal medicine "Sho-saiko-to" (TJ-9). As interstitial pneumonia is also induced by granulocyte colony-stimulating factor (G-CSF), we examined the effects of TJ-9 on G-CSF production in peripheral blood mononuclear cells. In patients with hepatitis B or C, G-CSF production in the absence of any stimulation was significantly lower than healthy controls (p < 0.01). G-CSF production increased along with the increase of TJ-9 levels, and this could induce excessive production of G-CSF in hepatitis C patients, and this may be a cause of interstitial pneumonia.

Anti-Inflammatory Agents, Non-Steroidal↗

Neovascularization of the intestinal graft transplanted in subcutaneous pocket in rats.

Clinically, the intestinal graft can survive without blood supply through its vascular pedicle for a certain period after transplantation, which is generally considered to be due to newly formed vessels from the surrounding tissue to the graft. Vascular synthesis from the surrounding tissue to the pedicled intestinal graft, transplanted subcutaneously was studied in rat model. Both the carbon dye infusion technique and hematoxylin-eosin stain were employed. After transplantation of the intestine, the number and diameter of carbon stained vessels were scored on days 2, 5, 7, 10, 14, 28, and 56, when the pedicle was ligated. All the histological specimens of the intestinal grafts were analyzed and then classified into three phases depending on the extent of surviving mucosa: 'necrosis', no live mucosa were observed; 'incomplete take', some islands of mucosa were alive; and 'complete take', all mucosa were alive. We characterized the relationship between the changes of the newly formed (carbon-dyed) vessels and the three histological phases. At 'necrosis', the newly formed vessels were rare and did not reach the intestinal graft. At 'incomplete take', random thin vascular networks were observed and some of them reached the graft. Some specimens were in the 'incomplete take' phase. At 'complete take', regular large vascular networks were observed. This transformation of the vascular networks seemed to reduce the the resistance of the vascular flow and to finally lead to the 'complete take' of the graft.

Animals↗

Retinopathy identifies marked restriction of coronary flow reserve in patients with diabetes mellitus.

OBJECTIVES: This study sought to assess the differences in coronary flow reserve in patients with and without diabetic retinopathy. BACKGROUND: Microvascular abnormalities throughout the body and impairment of coronary flow reserve have been described in patients with diabetes mellitus. However, the relation between diabetic retinopathy and coronary microvascular disease has not been investigated. METHODS: The study included 29 patients with diabetes mellitus (18 with and 11 without diabetic retinopathy) and 15 control patients with chest pain and normal coronary arteries. Diabetic retinopathy was nonproliferative in all 18 patients with this disorder (8 had background, 10 preproliferative retinopathy). Five minutes after injection of 3 mg of isosorbide dinitrate, phasic flow velocities were recorded in the proximal segment of the angiographically normal left anterior descending coronary artery at rest and during hyperemia (0.14 mg/kg body weight per min of adenosine infused intravenously) using a 0.014-in. 15-MHz Doppler guide wire. Coronary blood flow was calculated, and coronary flow reserve was obtained from the hyperemic/baseline flow ratio. RESULTS: Coronary blood flow was significantly lower during hyperemia ([mean +/- SD] 107 +/- 23 and 116 +/- 18 vs. 136 +/- 17 ml/min, respectively) and higher at baseline (58 +/- 16 and 45 +/- 12 vs. 37 +/- 10 ml/min, respectively) in diabetic patients with and without retinopathy than in control subjects (p < 0.05 for both diabetic groups). As a result, coronary flow reserve in both groups of diabetic patients was significantly lower than in control patients (1.9 +/- 0.4 and 2.8 +/- 0.3 vs. 3.3 +/- 0.4, respectively, p < 0.01 for both diabetic groups), and its reduction was greater in patients with than without retinopathy (p < 0.01). Furthermore, in patients with diabetic retinopathy, maximal hyperemic coronary flow (102 +/- 11 vs. 114 +/- 16 ml/min, p < 0.05) and flow reserve (1.6 +/- 0.2 vs. 2.3 +/- 0.2, p < 0.01) were significantly lower in those with preproliferative than background retinopathy. CONCLUSIONS: Coronary flow reserve is significantly restricted in patients with diabetes mellitus, and its reduction is more marked in those with diabetic retinopathy, especially in advanced retinopathy. Thus, diabetic retinopathy should identify marked restriction of coronary flow reserve in patients with diabetes mellitus.

Adult↗

Echocardiographic estimation of left ventricular cavity area with a newly developed automated contour tracking method.

Development of an automated contour tracking method provides detection and tracking of the endocardial boundary using the energy minimization method without tracing a region of interest. The purpose of this study was to compare the automated contour tracking method and manually drawn methods for the measurement of left ventricular cavity areas and fractional area change. Apical four-chamber view was visualized and recorded for off-line analysis in 11 patients by means of two-dimensional echocardiography. The automated contour tracking method automatically traces the endocardial border from the recorded images and calculates left ventricular cavity areas (end-diastole and end-systole) and fractional area change. In the same images selected as end-diastole and end-systole in the automated contour tracking method, left ventricular endocardial border was manually traced to calculate left ventricular cavity areas and fractional area change. Both methods were compared by linear regression analysis for the measurement of cavity areas and fractional area change. Left ventricular areas measured by the automated contour tracking method showed an excellent correlation with those by the manual method (end-diastole: r = 0.99, y = 0.83x + 2.6; standard error of the estimate = 1.5 cm2; end-systole: r = 0.99, y = 0.96x -0.8, standard error of the estimate = 1.2 cm2). The mean differences between the automated contour tracking and manual methods were -3.1 +/- 5.1 cm2 and -1.6 +/- 2.4 cm2 at end-diastole and end-systole, respectively. Fractional area change determined by the automated contour tracking method correlated well with that by the manual method (r = 0.95, y = 1.17x -6.5, standard error of the estimate = 3.4%). The mean difference between the automated contour tracking and manual methods was -0.8% +/- 7.1%. In conclusion, a newly developed automated contour tracking method correlates highly with the manual method for the estimation of left ventricular cavity areas and fractional area change in high-quality images. This suggests that this new technique may be useful in the automated quantitation of left ventricular function in patients with high-quality images with no dropout and no intercavity artifact or structure.

Echocardiography↗

Introduction of solvent-accessible surface area in the calculation of the hydrophobicity parameter log P from an atomistic approach.

A conventional atomistic approach of estimating molecular hydrophobicity (log P) was improved by taking into account the proximity effect of substituent groups as well as the importance of solute-solvent interaction in the partition phenomena. The new method reassigns atomic parameters when the molecule is fully exposed to surrounding solvent. Each atom in a molecule contributes to the log P by an amount of its atomic parameter multiplied by the degree of exposure to the surrounding solvent. This degree of exposure is calculated from the solvent-accessible surface area (SASA). In carrying out actual calculations, the necessary parameters were determined with the log P values of 500 compounds that were used as training data. This method, which may be called SASA-scaled atomistic method, gave satisfactory results when compared with the original method of estimating log P from atomic parameters. The ability of the new method to predict log P for compounds other than those used as the training data was also tested. The newly proposed SASA-scaled atomistic method was also compared with other methods available for the calculation of log P. The SASA-scaled atomistic method gave better estimations from fewer training data. Finally, the ability of the proposed method to predict differences in log P for steric isomers was tested. The new method was superior to other methods, including CLOGP, a widely accepted method of estimating log P for a variety of compounds.

Chemistry, Pharmaceutical↗

Nucleolar organizing regions in primary intracranial malignant lymphomas.

Twenty-two non-immunocompromised patients with primary intracranial malignant lymphomas were examined on surgical material by using an argyrophilic method for the demonstration of nucleolar organizer regions as Ag-NORs. The histopathological classifications of 22 patients included 3 small lymphocytic, 7 small cleaved, 9 large cell. 1 mixed large and small, and 2 small non-cleaved type. The numbers of Ag-NOR of malignant lymphoma patients varied from 1.36 to 5.02 (mean 3.46 +/- 0.25). The mean Ag-NOR numbers in the histopathological subtypes were small lymphocytic 1.63, small cleaved 3.18, large 4.21, mixed large and small 3.47, and small non-cleaved 3.78. The number of Ag-NORs in small lymphocytic type was significantly less than small cleaved or large cell type (p < 0.05). The small cleaved type also had a smaller Ag-NOR number than the large cell type (p < 0.05). Except for two patients who had postoperative deterioration, 20 patients received postoperative irradiation ranging from 36 to 54 Gy (median, 46 Gy). Sixteen patients had complete response to radiotherapy, and 4 had good partial response. Ten patients had tumor recurrence within the remission period of 3 months to 7 years and 10 months (median 4.8 months). Three patients with intracranial relapse at a remote site had a significantly longer remission period (mean 57.3 months) than 7 with local relapse (mean 6.29 months), p < 0.05. The mean Ag-NOR number of the short and long remission period were 3.13 +/- 0.34 and 3.8 +/- 0.80, respectively. No significant difference was found between these two groups. The survival period was 3.2 months to 12 years (median 20 months). The Ag-NOR numbers of survival period less than or more than 20 months were 3.62 +/- 0.40 and 3.27 +/- 0.37, respectively. The Ag-NOR numbers did not correlate with either the remission or the survival period. These results indicate that Ag-NOR numbers may correlate with the histopathologic types, but not with the prognosis of primary intracranial malignant lymphomas.

Adult↗

Application of a deductive database system to search for topological and similar three-dimensional structures in protein.

A deductive database system PACADE (Protein Atomic Coordinate Analyzer with Deductive Engine) has been developed for protein structure analysis. With this system, super-secondary structures described in logical and declarative rules can be retrieved effectively. For protein structure analysis, comparison of local structures in different proteins is a necessary mean. A function to search for similar structures has, therefore, been added to the PACADE system. We describe herein the result of searches for the same topological structures and three-dimensionally similar ones. A user of PACADE can select these two levels of similarity by changing parameters. This function enables the inference system to retrieve similar structures, according to the restraints of variables defined by the user. Similar super-secondary structures among proteins can be searched for automatically, which is useful for protein structure analysis. The retrieved similar super-secondary structures can serve as criteria for protein spatial alignment.

Algorithms↗

Structure of the ascidian, Halocynthia roretzi, troponin C gene.

Two distinct cDNAs encoding troponin C (TnC) isoforms were isolated from the ascidian, Halocynthia roretzi. One is expressed in adult body wall smooth muscle and heart muscle, and the other in larval striated muscle. The H. rorezti gene is composed of 7 exons separated by 6 introns, and Southern blot analysis showed that TnC is a single copy gene product. The two isoforms of TnC were derived through the alternative splicing of the third exon.

Age Factors↗

A survey of genes expressed in mouse embryonal carcinoma F9 cells: characterization of expressed sequence tags matching no known genes.

We prepared 2,132 expressed sequence tags (ESTs) from undifferentiated mouse embryonal carcinoma F9 cells and found that 1,416 match known gene and/or protein sequences [Nishiguchi et al. (1996) J. Biochem. 119, 749-767]. To obtain information on the functions of the remaining 716 unidentified ESTs and to develop a system for characterizing ESTs matching no known genes, we analyzed their sequences by (i) repeated database searches, using the BLASTN, BLASTX, TBLASTX, and FASTA programs, (ii) using computer programs developed or modified for this work, such as the WFASTA, ORFTRNS, and MFASTA programs, together with the DBPROSITE and GRAIL programs, and (iii) examining the expression patterns of the corresponding mRNAs in F9 cells and several organs of adult mice, using the digoxigenin-labeled dot-blot method. We found that 216 of the 716 ESTs match known gene and/or protein sequences, and 307 show significant similarities to these sequences, with a Poisson p-value < 0.01. The strategy and usefulness of such analysis for characterizing unidentified ESTs are discussed.

Animals↗

Primary structure of troponin I isoforms from the ascidian Halocynthia roretzi.

The solitary ascidian Halocynthia roretzi possesses three types of muscle: the larval tail striated muscle, the adult heart striated muscle, and the adult body wall smooth muscle. The troponin complex is observed in all types of muscle, and the isoform sequences and expression patterns of two of the three troponin components, troponins C and T, have been reported. In this study, we have determined cDNA sequences of the three TnI isoforms from H. roretzi. One of the three isoforms (adult TnI), expressed in adult body wall smooth muscle and heart muscle, was composed of 173 amino acids, being similar to vertebrate fast and slow skeletal TnIs in length. The other two isoforms (larval TnI alpha and TnIbeta) were isolated from a cDNA library of larvae. Both larval TnIs were composed of 142 amino acids, with truncation amounting to ca. 30 amino acid residues at the C-termini. These larval TnIs are the smallest known TnIs. The position of the last intron of these TnIs was also determined. When compared with vertebrate TnI genes, the last intron of the ascidian adult TnI gene is located at 6 nucleotides downstream, and the introns of the two larval TnIs are positioned at 9 nucleotides upstream. These results suggest that H. roretzi TnI is encoded by at least three genes.

Amino Acid Sequence↗

Lateral ray polydactyly: a case of duplicated metatarsal with normal phalanges.

Lateral ray polydactyly of the foot is morphologically classified on the basis of the external appearance and the anatomic patterns of bony structures. Classification is difficult when the level of duplication is not apparent. We encountered a case of a duplicated metatarsal with no duplication of phalanges. The anomaly was considered to be a case of polydactyly because there were supernumerous metatarsals. On the basis of embryological failure, limb malformations are classified into several categories, and polydactyly belongs to that of duplication. There are, however, some malformations that are difficult to classify clearly. We considered our case to be a result of duplication followed by fusion of the digits.

Child, Preschool↗

[Acute respiratory failure associated with G-CSF-induced leukocyte recovery in three patients with preceding infection].

Acute respiratory failure (ARF) occurred at the time of leukocyte recovery promoted by granulocyte colony-stimulating factor (G-CSF) in three patients with the preceding infection (S. aureus pneumonia, varicella zoster, and P. aeruginosa bacteremia, respectively) which had developed during leukopenia after cancer chemotherapy. G-CSF was used for 4 to 6 days, and the leukocyte counts at onset of ARF were 19,300/microliter, 11,300/microliter, and 4,100/microliter, respectively. All of the three patients received high-dose methylprednisolone and the artificial respiration was used in two. Consequently two patients responded well and survived, but one died of respiratory failure 2 weeks after occurrence of ARF. Autopsy of the dead case revealed mild interstitial pneumonia in the both lungs together with bacterial pneumonia in the right lobe. These cases indicate that G-CSF-induced leukocyte recovery can cause severe ARF in patients with precending infection. Therefore, G-CSF should be administered very carefully to granulocytopenic patients with infection.

Acute Disease↗

Enhanced interleukin-8 production by cultured Chang liver cells subjected to ethanol exposure and subsequent stimulation with tumor necrosis factor-alpha.

We investigated the production of interleukin-8 (IL-8) and chemotactic activity released from Chang liver cells subjected to long-term treatment with ethanol (Et) and subsequent stimulation with tumor necrosis factor-alpha (TNF-alpha). Chang liver cells were cultured in the presence of 5, 50 or 100 mmol/l Et for 4 weeks and then treated with recombinant TNF-alpha (1, 10, 100 U/ml). The culture supernatants were assayed for IL-8 using a sandwich ELISA and chemotactic activity was measured using a chemotactic chamber. Total RNA was also extracted from these cells and IL-8 mRNA was assayed by RT-PCR. In addition, TNF-receptor expression on the Et-treated cells was analyzed by flow cytometry. IL-8 levels in supernatants of cells stimulated with 100 U/ml of TNF-alpha for 48 h rose significantly with increasing concentrations of Et and values obtained were as follows: 4,918 +/- 244.4 pg/ml at 0 mmol/l Et, 5,335 +/- 266.2 pg/ml at 5 mmol/l Et, 8,726 +/- 873.4 pg/ml at 50 mmol/l Et and 9,134 +/- 866.0 pg/ml at 100 mmol/l Et. The chemotactic activity also increased with increasing concentrations of Et and was almost completely suppressed by anti-IL-8 antibody. Using semiquantitative analysis of radioactivity of IL-8 mRNA using a 32P gamma ATP-labeled primer for IL-8 mRNA, Et-treated cells were shown to have markedly higher levels of radioactivity than untreated cells. In addition, TNF-receptor expression was significantly higher in cells treated with 100 mmol/l Et. These data suggest that long-term Et treatment of Chang liver cells stimulated with TNF-alpha may enhance transcription of the IL-8 gene with up-regulation of the TNF receptor.

Antibodies↗

Regulation of eukaryotic abasic endonucleases and their role in genetic stability.

Abasic (AP) sites in DNA arise from spontaneous reactions or the action of DNA glycosylases and represent a loss of genetic information. The AP sites can be mutagenic or cytotoxic, and their repair is initiated by class II AP endonucleases, which incise immediately 5' to AP sites. The main enzyme of S. cerevisiae. Apn1, provides cellular resistance to oxidants (e.g., H2O2) or alkylating agents, and limits the spontaneous mutation rate. AP endonucleases from other species can replace Apn1 function in yeast to different extents. We studied the main human enzyme, Ape, with respect to its incision specificity in vitro and the expression of the APE gene in vivo. The results suggest that Ape evolved to act preferentially on AP sites compared to deoxyribose fragments located at oxidative strand breaks and that the incision modes of Ape and Apn1 may be fundamentally different. We also defined the functional APE promoter, and showed that APE expression is transiently downregulated during the regeneration of epidermis after wounding. This latter effect may lead to a window of vulnerability for DNA damage and perhaps mutagenesis during the healing of epidermal and other wounds. Such unexpected effects on the expression of DNA repair enzymes need to be taken into account in analyzing the susceptibility of different tissues to carcinogens.

DNA Damage↗

Applying Association Rule Discovery Algorithm to Multipoint Linkage Analysis.

Knowledge discovery in large databases (KDD) is being performed in several application domains, for example, the analysis of sales data, and is expected to be applied to other domains. We propose a KDD approach to multipoint linkage analysis, which is a way of ordering loci on a chromosome. Strict multipoint linkage analysis based on maximum likelihood estimation is a computationally tough problem. So far various kinds of approximate methods have been implemented. Our method based on the discovery of association between genetic recombinations is so different from others that it is useful to recheck the result of them. In this paper, we describe how to apply the framework of association rule discovery to linkage analysis, and also discuss that filtering input data and interpretation of discovered rules after data mining are practically important as well as data mining process itself.

Journal Article↗

[Evaluation of left ventricular ejection fraction using an automated contour tracking method: comparison with equilibrium radionuclide angiography].

A recently developed contour tracking method provides automated edge detection of left ventricular endocardium without a region of interest. The accuracy of this automated contour tracking (ACT) method in the evaluation of left ventricular ejection fraction was assessed in 20 patients (16 males and 4 females, mean age 58 years) using both the ACT method and equilibrium radionuclide angiography. Ejection fractions measured by the ACT method correlated well with those measured by equilibrium radionuclide angiography (y = 0.8x + 11.9, r = 0.91, SEE = 4.0%, p < 0.01). The ACT method provides an accurate estimate of left ventricular ejection fraction.

Echocardiography↗

Hepatitis B virus carriers in the treatment of malignant lymphoma: an epidemiological study in Japan.

BACKGROUND: Hepatitis B after the withdrawal of cytotoxic chemotherapy in hepatitis B virus (HBV) carriers is well known and may lead to fatal hepatic failure. We retrospectively analyzed the prevalence of HBV carriers, the incidence, and the risk factors of hepatitis B in the treatment of malignant lymphoma. PATIENTS AND METHODS: HBV carriers were defined as patients with positive HBs-antigen, either with normal or abnormal serum aminotransferase level at patient presentation. Questionnaires to the members of the Japan Lymphoma Treatment Study Group included general information, details about HBV carriers, and further information about hepatitis B. RESULTS: Among 1380 patients collected from eight institutions, 45 patients (3.26%) were determined to be HBV carriers, Hepatitis B developed in 17 of the HBV carrying patients (37.8%). Seven of those 17 (41.2%) died of hepatic failure. Hepatitis developed at a high rate in patients who were negative for HBe-antigen (50%), and who had received second- or third-generation chemotherapy (63.2%). CONCLUSION: We confirmed that hepatitis B developed with high frequency in HBV carriers with malignant lymphoma. Moreover, hepatitis often resulted in fatal hepatic failure. It is necessary to prevent the hepatitis B developing in HBV carriers when receiving intensive chemotherapy for malignant lymphoma.

Adolescent↗