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H Tada

Publications and source records attributed to H Tada.

At least 37 records · Page 2Linked to original sources

Development of liver dysfunction after delivery is possibly due to postpartum autoimmune hepatitis. A report of three cases.

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases involve transient dysfunction of affected organs. We examined three patients who developed liver dysfunction after delivery. They were all diagnosed with definite or probable autoimmune hepatitis using the scoring system of the International Autoimmune Hepatitis Group. Moreover, all of them had anti-CYP2D6 antibodies detected by a sensitive radioligand assay. Our findings strongly suggest that liver dysfunction is induced by postpartum autoimmune hepatitis, and clinicians should be aware of this disease.

Adult↗

Sensor system using polarization analysis method to monitor oil-on-water in water purification plants and rivers.

Some 80% of accidental pollution in river water is caused by oil spills. Oil spills can cause serious damage such as suspension of water intake at water purification plants and major harm to ecosystems in the lower reaches of rivers. This is because oil-on-water tends to spread easily, quickly exacerbating the damage. To address this problem, an automated, continuous sensor system with high sensitivity can be used for early detection of spill accidents. We have developed a sensor system for detecting oil-on-water based on a polarization analysis method. Its advantages include: a) no direct contact with sample water; b) minimal maintenance; c) largely unaffected by foreign matter and waves on the water surface; and d) much higher sensitivity than simple visual observation. This paper describes the measurement principle and configuration of the sensor system, and discusses the results of sensitivity tests and tests on the influence of water turbidity, foreign matter and waves. We will also consider some of the limitations of the new system.

Environmental Monitoring↗

Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5.

Novel low molecular weight spirodiketopiperazine derivatives which potently inhibit R5 human immunodeficiency virus type 1 (HIV-1) infection through their antagonistic effects on CCR5 were identified. One such compound E913 (M(r) 484) specifically blocked the binding of macrophage inflammatory protein-1alpha (MIP-1alpha) to CCR5 (IC(50) 0.002 microm) and MIP-1alpha-elicited cellular Ca(2+) mobilization (IC(50) approximately 0.02 microm). E913 potently inhibited the replication of laboratory and primary R5 HIV-1 strains as well as various multidrug-resistant monocyte/macrophage tropic (R5) HIV-1 at IC(50) values of 0.03 to 0.06 microm. E913 was inactive against T cell tropic (X4) HIV-1; however, when combined with a CXCR4 antagonist AMD-3100, E913 potently and synergistically inhibited the replication of dualtropic HIV-1 and a 50:50 mixture of R5 and X4 HIV-1. Antagonism in anti-HIV-1 activity was not seen when E913 was combined with the reverse transcriptase inhibitor zidovudine or protease inhibitors. E913 proved to compete with the binding of antibodies to CCR5 which recognize the C-terminal half of the second extracellular loop (ECL2B) of CCR5. E913 and its analogs are acid-resistant and orally bioavailable in rodents. These data warrant that spirodiketopiperazine derivatives be further developed as potential therapeutics for HIV-1 infection.

Animals↗

Preparation of potent cytotoxic ribonucleases by cationization: enhanced cellular uptake and decreased interaction with ribonuclease inhibitor by chemical modification of carboxyl groups.

Carboxyl groups of bovine RNase A were amidated with ethylenediamine (to convert negative charges of carboxylate anions to positive ones), 2-aminoethanol (to eliminate negative charges), and taurine (to keep negative charges), respectively, by a carbodiimide reaction. Human RNase 1 was also modified with ethylenediamine. Surprisingly, the modified RNases were all cytotoxic toward 3T3-SV-40 cells despite their decreased ribonucleolytic activity. However, their enzymatic activity was not completely eliminated by the presence of excess cytosolic RNase inhibitor (RI). As for native RNase A and RNase 1 which were not cytotoxic, they were completely inactivated by RI. More interestingly, within the cytotoxic RNase derivatives, cytotoxicity correlated well with the net positive charge. RNase 1 and RNase A modified with ethylenediamine were more cytotoxic than naturally occurring cytotoxic bovine seminal RNase. An experiment using the fluorescence-labeled RNase derivatives indicated that the more cationic RNases were more efficiently adsorbed to the cells. Thus, it is suggested that the modification of carboxyl groups could change complementarity of RNase to RI and as a result endow RNase cytotoxicity and that cationization enhances the efficiency of cellular uptake of RNase so as to strengthen its cytotoxicity. The finding that an extracellular human enzyme such as RNase 1 could be effectively internalized into the cell by cationization suggests that cationization is a simple strategy for efficient delivery of a protein into cells and may open the way of the development of new therapeutics.

3T3 Cells↗

Gastric distension-induced pyloric relaxation: central nervous system regulation and effects of acute hyperglycaemia in the rat.

1. The pylorus plays an important role in the regulation of gastric emptying. In addition to the autonomic neuropathy associated with long-standing diabetes, acute hyperglycaemia per se has effects on gastric emptying. In this study, the role of the central nervous system in modulating the effects of hyperglycaemia on gastric distension-induced pyloric relaxation was investigated. 2. Gastric distension-induced pyloric relaxation was significantly reduced by subdiaphragmatic vagotomy, hexamethonium (20 mg kg(-1)) and N (G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1)), a nitric oxide synthase (NOS) biosynthesis inhibitor, in anaesthetized rats. In contrast, neither splanchnectomy nor guanethidine (5 mg kg(-1)) had an effect. 3. An intravenous (I.V.) infusion of D-glucose (20 %) for 30 min, which increased blood glucose concentrations from 5.4 to 12.8 mM, significantly inhibited gastric distension-induced pyloric relaxation. 4. An intracerebroventricular (I.C.V.) injection of D-glucose (3 micromol) also significantly inhibited gastric distension-induced pyloric relaxation without affecting peripheral blood glucose concentrations. 5. I.V. infusion of D-glucose significantly elevated hypothalamic neuropeptide Y (NPY) concentrations. 6. Intracerebroventricular (I.C.V.) administration of NPY (0.03--3 nmol) and a Y1 receptor agonist, [leu(31), pro(34)] NPY (0.03--3 nmol), significantly inhibited gastric distension-induced pyloric relaxation in a dose-dependent manner. 7. I.C.V. administration of a Y1 receptor antagonist, BIBP 3226 (30 nmol), and of a NPY antibody (titre 1:24 000, 3 microl) abolished the inhibitory effects of hyperglycaemia on gastric distension-induced pyloric relaxation. 8. Taken together, these findings suggest that gastric distension-induced pyloric relaxation is mediated via a vago-vagal reflex and NO release. Acute hyperglycaemia stimulates hypothalamic NPY release, which, acting through the Y1 receptor, inhibits gastric distension-induced pyloric relaxation in rats exposed to acute elevations in blood glucose concentrations.

Acute Disease↗

Canine ventricular myocytes possess a renin-angiotensin system that is upregulated with heart failure.

Ventricular pacing leads to a dilated myopathy in which cell death and myocyte hypertrophy predominate. Because angiotensin II (Ang II) stimulates myocyte growth and triggers apoptosis, we tested whether canine myocytes express the components of the renin-angiotensin system (RAS) and whether the local RAS is upregulated with heart failure. p53 modulates transcription of angiotensinogen (Aogen) and AT(1) receptors in myocytes, raising the possibility that enhanced p53 function in the decompensated heart potentiates Ang II synthesis and Ang II-mediated responses. Therefore, the presence of mRNA transcripts for Aogen, renin, angiotensin-converting enzyme, chymase, and AT(1) and AT(2) receptors was evaluated by reverse transcriptase-polymerase chain reaction in myocytes. Changes in the protein expression of these genes were then determined by Western blot in myocytes from control dogs and dogs affected by congestive heart failure. p53 binding to the promoter of Aogen and AT(1) receptor was also determined. Ang II in myocytes was measured by ELISA and by immunocytochemistry and confocal microscopy. Myocytes expressed mRNAs for all the constituents of RAS, and heart failure was characterized by increased p53 DNA binding to Aogen and AT(1). Additionally, protein levels of Aogen, renin, cathepsin D, angiotensin-converting enzyme, and AT(1) were markedly increased in paced myocytes. Conversely, chymase and AT(2) proteins were not altered. Ang II quantity and labeling of myocytes increased significantly with cardiac decompensation. In conclusion, dog myocytes synthesize Ang II, and activation of p53 function with ventricular pacing upregulates the myocyte RAS and the generation and secretion of Ang II. Ang II may promote myocyte growth and death, contributing to the development of heart failure.

Actins↗

The difference in E-cadherin expression between nonvascularized and vascularized nerve grafts: study in the rat sciatic nerve model.

BACKGROUND: We investigated the expression of E-cadherin during nerve regeneration after nonvascularized and vascularized nerve grafts. MATERIALS AND METHODS: We used the rat sciatic nerve model. E-cadherin expression was detected by Western blot analysis and immunofluorescent staining with anti E-cadherin monoclonal antibody. The level of E-cadherin expression was calculated as the amount relative to that of E-cadherin expression of normal control nerve. Furthermore, repair of the neural tissue structure was examined by toluidine blue staining. RESULTS: In both cases, the level of E-cadherin expression decreased at first, and then gradually increased. The maximum level was 1.61 +/- 0.066-fold in the nonvascularized nerve graft and 2.254 +/- 0.071-fold in the vascularized nerve graft. From the 1st to the 16th postoperative weeks, the level of E-cadherin expression in the vascularized nerve graft was significantly higher than that in the nonvascularized nerve graft. In the immunofluorescent staining, E-cadherin expression was almost negative or decreased immediately after the operation, but the degree of expression was gradually increased in Schwann cells. The degree of E-cadherin expression in the vascularized nerve graft was greater than that in the nonvascularized nerve graft. In toluidine blue staining, the velocity of tissue repair was more rapid in the vascularized nerve graft than in the nonvascularized graft. CONCLUSION: These results demonstrate that the E-cadherin expression of grafted nerve was increased during the nerve regeneration, and the expression was mainly observed in Schwann cells. Because the level of E-cadherin expression was significantly higher in the vascularized nerve graft than in the nonvascularized nerve graft, the level of E-cadherin expression may affect the rapidity of nerve regeneration.

Animals↗

Intra-arterial delivery of a recombinant adenovirus does not increase gene transfer to tumor cells in a rat model of metastatic colorectal carcinoma.

Hepatic artery infusion of adenoviral vectors has been shown to increase transduction of certain hepatocellular malignancies in preclinical studies. In addition, clinical trials have begun evaluating the efficacy of gene transfer of cytotoxic genes to metastatic colorectal tumors through hepatic artery infusion. Here we evaluate the extent of gene expression and therapeutic effect following various routes of administration of recombinant adenovirus in a rat model of metastatic colorectal carcinoma. We administered adenovirus (AdCMVlacZ) to rats with established colorectal metastases through infusion into the hepatic artery, intravenous infusion, or direct injection into a tumor. Intravenous administration resulted in transduction of hepatocytes, but not tumor cells. Hepatic arterial administration failed to substantially increase transduction of tumor cells. In addition, ligation of the hepatic artery following infusion of adenovirus or the addition of lipiodol infusion had no effect on the transduction of tumor cells. We administered AdCMVp53 by direct injection into tumors, intravenous administration, or hepatic artery infusion to evaluate the delivery of a therapeutic gene. Direct injection of AdCMVp53 into established hepatic colorectal metastases resulted in a therapeutic response in comparison with both hepatic arterial and intravenous infusion of vector. These preclinical studies fail to support a strategy of infusion through the hepatic artery of recombinant adenovirus targeting tumor cells in the treatment of colorectal cancer liver metastases.

Adenoviridae↗

Effects of dioxins and polychlorinated biphenyls (PCBs) on thyroid function in infants born in Japan--the second report from research on environmental health.

Dioxins (PCDD + PCDF) and polychlorinated biphenyl (PCB) are potentially hazardous compounds and have structural similarity to thyroid hormones. Our research group on "Dioxins and PCB in Human Milk" was organized in 1997 and has been active for the past three years. We collected breast milk from 80 mothers living in Tokyo, Saitama, Ishikawa and Osaka Prefecture in Japan at 5, 30, 150, 300 postpartum days and measured PCDDs, PCDFs and PCBs during 1998-1999. We added another 20 prefectures and cities during 1999-2000. Breast milk was obtained from 415 mothers at 30 postpartum days (breast-feeding group). Blood was taken from infants who were breast-fed at the age of 1 year for evaluation of thyroid and immune functions. Blood was also taken from 53 infants who were bottle-fed (bottle-feeding group) as a control. Serum T4, T3, FT4 and TSH levels in the breast-feeding (n = 337) and bottle-feeding (n = 53) groups were within normal ranges and were not significantly different between the two groups. Although there were a large geographic differences of dioxins and co-PCB content in breast milk, there were no differences in serum T4, T3, FT4, TSH levels and no significant correlation between the mean serum levels of TSH and TEQ in breast milk. There was a significant correlation between serum TSH at 1 year of age and that from blood on dried filter paper TSH at 5 days of age. We concluded that dioxin intake from breast milk in Japanese infants did not impair thyroid function. However, long-term effects remain to be evaluated.

Adult↗

Prognosis of non-small cell lung cancer patients with positive pleural lavage cytology after a thoracotomy: results of the survey conducted by the Japan Clinical Oncology Group.

OBJECTIVE: The purpose of this study was to clarify the prognosis of non-small cell lung cancer patients without pleural effusion whose intrapleural cancer cells were detected by a cytologic examination of pleural lavage fluid obtained immediately after a thoracotomy. METHOD: A questionnaire survey on the survival of the patients with positive pleural lavage cytology from January 1985 to December 1994 was performed by the Japan Clinical Oncology Group. RESULTS: According to the data collected from 15 institutions, 1890 non-small cell lung cancer patients without pleural effusion underwent pleural lavage cytology immediately after thoracotomy and 142 (7.8%) of them were found to have intrapleural cancer cells detected by the cytological analysis. The information of survival on 113 patients was available. This comprised of 64 males and 49 females with a mean age of 64.6 years. The predominant histologic type was adenocarcinoma (74%). Out of these 113 patients, 109 (97%) underwent a surgical resection. The 5-year survival rate was 30% in all patients, 49% in pathological stage I (n=35), 23% in stage II (n=20) and 26% in stage IIIA (n=34). CONCLUSION: Patients with a positive pleural lavage cytology in pathological stage I or II appear to have a poor 5-year survival rate.

Aged↗

Double potentials along the ablation line as a guide to radiofrequency ablation of typical atrial flutter.

OBJECTIVES: The purpose of this study was to determine the characteristics of double potentials (DPs) that are helpful in guiding ablation within the cavo-tricuspid isthmus. BACKGROUND: Double potentials have been considered a reliable criterion of cavo-tricuspid isthmus block in patients undergoing radiofrequency ablation of typical atrial flutter (AFL). However, the minimal degree of separation of the two components of DPs needed to indicate complete block has not been well defined. METHODS: Radiofrequency ablation was performed in 30 patients with isthmus-dependent AFL. Bipolar electrograms were recorded along the ablation line during proximal coronary sinus pacing at sites at which radiofrequency ablation resulted in incomplete or complete isthmus block. RESULTS: Double potentials were observed at 42% of recording sites when there was incomplete isthmus block, compared with 100% of recording sites when the block was complete. The mean intervals separating the two components of DPs were 65 +/- 21 ms and 135 +/- 30 ms during incomplete and complete block, respectively (p < 0.001). An interval separating the two components of DPs (DP(1-2) interval) <90 ms was always associated with a local gap, whereas a DP(1-2) interval > or =110 ms was always associated with local block. When the DP(1-2) interval was between 90 and 110 ms, an isoelectric segment within the DP and a negative polarity in the second component of the DP were helpful in indicating local isthmus block. A DP(1-2) interval > or =90 ms with a maximal variation of 15 ms along the entire ablation line was an indicator of complete block in the cavo-tricuspid isthmus. CONCLUSIONS: Detailed analysis of DPs is helpful in identifying gaps in the ablation line and in distinguishing complete from incomplete isthmus block in patients undergoing radiofrequency ablation of typical AFL.

Action Potentials↗

Differentiation of atypical atrioventricular node re-entrant tachycardia from orthodromic reciprocating tachycardia using a septal accessory pathway by the response to ventricular pacing.

OBJECTIVES: The purpose of this study was to determine whether the response to ventricular pacing during tachycardia is useful for differentiating atypical atrioventricular node re-entrant tachycardia (AVNRT) from orthodromic reciprocating tachycardia (ORT) using a septal accessory pathway. BACKGROUND: Although it is usually possible to differentiate atypical AVNRT from ORT using a septal accessory pathway, a definitive diagnosis is occasionally elusive. METHODS: In 30 patients with atypical AVNRT and 44 patients with ORT using a septal accessory pathway, the right ventricle was paced at a cycle length 10 to 40 ms shorter than the tachycardia cycle length (TCL). The ventriculo-atrial (VA) interval and TCL were measured just before pacing. The interval between the last pacing stimulus and the last entrained atrial depolarization (stimulus-atrial [S-A] interval) and the post-pacing interval (PPI) at the right ventricular apex were measured on cessation of ventricular pacing. RESULTS: All 30 patients with atypical AVNRT and none of the 44 patients with ORT using a septal accessory pathway had an S-A-VA interval >85 ms and PPI-TCL >115 ms. CONCLUSIONS: The S-A-VA interval and PPI-TCL are useful in distinguishing atypical AVNRT from ORT using a septal accessory pathway.

Adult↗

E-cadherin expression in wound healing of mouse skin.

BACKGROUND: E-cadherin has been studied extensively in other systems but little attention has been paid to its role in wound healing. We investigated E-cadherin expression in epithelial wound healing in vivo by focusing on the migrating cells in the epithelial tongue and the mitotic cells in the non-injured side apart from the original wound edge. METHODS: Round full-thickness excisional wounds (6 mm in diameter) and full-thickness incisional wounds were prepared dorsally in mice. On various days after the operation, E-cadherin expression was examined by immunohistochemical staining using a monoclonal antibody specific for E-cadherin. RESULTS: In both models, the level of E-cadherin expression did not decrease on the 1st postoperative (P.O.) day. After the 2nd P.O. day, E-cadherin expression decreased in cells at a site 500 microm apart from the original wound edge. After the 3rd P.O. day, decreased expression was also observed in cells at the top and in the basal layer of the epithelial tongue. This decreased expression continued for 1 or 2 days after the meeting of the epithelial tongue. There was no significant difference in the expression of E-cadherin between two models. CONCLUSIONS: The results suggested that E-cadherin expression decreases in epithelial cells. This decrease may depend on the activity of migration and mitosis. In addition, the change was similar in both the excisional and incisional wounds.

Animals↗

The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia.

AIMS: A rare type of thymoma, micronodular thymoma with lymphoid B-cell hyperplasia, was recently reported by Suster and Moran. Thymic epithelial tumours with a similar pattern but with varied cytological features of the tumour cells are analysed. METHODS AND RESULTS: A total of 11 cases of thymic epithelial tumours characterized by micronodular proliferation of tumour cells separated by abundant lymphoid stroma with prominent germinal centres were reviewed clinicopathologically and examined immunohistochemically. The presence of Epstein-Barr virus (EBV) genome was also examined by in-situ hybridization. Based on the morphology of tumour epithelial cells, cases were subdivided into four groups: group 1 (two cases) having spindle epithelial cells; group 2 (two cases) showing an admixture of spindle and polygonal epithelial cells; group 3 (five cases) having polygonal epithelial cells, with mild to moderate cytological atypia in four cases, and group 4 (two cases) representing lymphoepithelioma-like carcinoma. The degree of cytological atypia and the number of tumour cells positive for MIB-1 and p53 gradually increased towards group 4. The abundant lymphoid stroma in all cases contained many CD20-positive B-cells and CD3 and CD45RO-positive T-cells. CD99-positive immature T-cells were present in all cases of groups 1 and 2 and in most cases of group 3, but not in both cases of group 4 tumours. IgG, IgM and IgD-positive plasma cells and lymphocytes were also present in all cases, more prominent in those of groups 3 and 4. The EBV genome was detected in only a few lymphocytes in five cases. CONCLUSIONS: The tumours in this series belong to a distinct category of thymic epithelial tumours and each of the above groups may constitute a spectrum in the continuum of cytological atypia. The aetiological relationship of EBV with these tumours could not be proved. The lymphoid B-cell hyperplasia may result from a host immune response and may suggest a favourable clinical course of this type of tumour.

Aged↗

Chrono and clinical pharmacokinetic study of tacrolimus in continuous intravenous administration.

BACKGROUND: The circadian variation of clinical pharmacokinetics of tacrolimus in kidney transplant recipients receiving continuous intravenous administration has not been clarified. The aim of this study was to evaluate the circadian variation of this drug in continuous intravenous administration, with regard to the dosing scheme for conversion from intravenous to oral therapy. METHODS: The blood concentration-time curve was studied in 10 living-related kidney transplant recipients, aged 18-51 years (mean, 36.5 years), 1 day before operation for preoperative oral administration, the third postoperative day for continuous intravenous administration and the sixth postoperative day at the conversion from intravenous to oral therapy. RESULTS: Although the total body clearance of daytime was slightly higher than that of night-time, the intravenous tacrolimus infusion maintained an adequate therapeutic blood concentration for 24 h. There were significant differences between the preoperative and the postoperative state in the area under the curve, total body clearance and bioavailability for the oral administration. The mean absolute bioavailability was 17.7% in preoperative and 11.1% in postoperative state, respectively and a large interindividual variation was confirmed in this parameter, which was 7.0-27.2% for preoperative and 6.4-22.0% for postoperative area under the curve, respectively. CONCLUSION: This study proposes that intravenous administration is a safe and appropriate method to achieve the required blood concentration in patients with various tacrolimus metabolism in the early post-transplant period. As the oral tacrolimus absorption was found to be variable between preoperative and postoperative states in identical patients, the conversion dosage cannot be calculated from preoperative oral or postoperative intravenous pharmacokinetics. Frequent blood concentration monitoring is needed to ensure safe treatment.

Administration, Oral↗

Role of transisthmus conduction intervals in predicting bidirectional block after ablation of typical atrial flutter.

INTRODUCTION: Complete bidirectional cavotricuspid isthmus block is the endpoint for ablation of typical atrial flutter. The purpose of this study was to determine whether the extent of prolongation of the transisthmus interval after ablation predicts complete bidirectional block. METHODS AND RESULTS: Fifty-seven consecutive patients underwent 60 ablation procedures for isthmus-dependent atrial flutter. The clockwise and counterclockwise transisthmus intervals were determined before and after ablation during pacing from the low lateral right atrium and the coronary sinus. Bidirectional block was achieved with ablation in 55 (96%) of 57 patients. The transisthmus intervals before ablation and after complete transisthmus block were 100.3 +/- 21.1 msec and 195.8 +/- 30.1 msec, respectively, in the clockwise direction (P < 0.0001), and 98.2 +/- 24.7 msec and 185.7 +/- 33.9 msec, respectively, in the counterclockwise direction (P < 0.0001). An increase in the transisthmus interval by > or = 50% in both directions after ablation predicted complete bidirectional block with 100% sensitivity and 80% specificity. The positive and negative predictive values were 89% and 100%, respectively. The diagnostic accuracy of a > or = 50% prolongation in the transisthmus interval was 92%. CONCLUSION: Prolongation of the transisthmus interval by > or = 50% in the clockwise and counterclockwise directions is associated with a high degree of diagnostic accuracy and an excellent negative predictive value in determining complete bidirectional transisthmus block. This may be a useful and simple adjunctive criterion for assessment of complete transisthmus conduction block.

Aged↗