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Biomedical subjects

H Tada

Publications and source records attributed to H Tada.

At least 163 records · Page 9Linked to original sources

An aldose reductase inhibitor prevents glucose-induced increase in transforming growth factor-beta and protein kinase C activity in cultured mesangial cells.

We investigated the effect of inhibition of a polyol pathway on the glucose-induced increase in transforming growth factor-beta (TGF-beta) production and activity of protein kinase C (PKC) in cultured human mesangial cells (MCs). The exposure of MCs to 33 mmol/l glucose resulted in an increase in TGFbeta production, measured by ELISA, compared with 5 mmol/l glucose. The glucose-induced increase in TGF-beta was prevented by concomitant incubation with epalrestat, an aldose reductase inhibitor (ARI), in a dose-dependent manner at a concentration of more than 10(-6) mol/l. Moreover, the glucose-induced enhancement of PKC activity in the membrane fraction of MCs was also abolished by epalrestat. The addition of epalrestat to MCs cultured with 5 mmol/l glucose showed no demonstrable effects on TGF-beta production and PKC activity. These results provide direct evidence for linkages between derangements in polyol pathway and glucose-induced overproduction of TGF-beta and enhancement of PKC activity in MCs. Accordingly, the effect of an ARI on these metabolic abnormalities in MCs may justify its clinical application for treatment of diabetic nephropathy.

Aldehyde Reductase↗

Antitumor vaccination effect of dendritic cells can be augmented by locally utilizing Th1-type cytokines from OK432-reactive CD4+ T cells.

In order to enhance the antitumor vaccination effect of dendritic cells (DC) pulsed with class I tumor peptide, we tried to utilize the local cytokine help of CD4+ T cells reactive to a streptococcal preparation OK432. DC were prepared from murine bone marrow cells by culture with both granulocyte/macrophage-colony-stimulating factor and interleukin(IL)-4. The peritumoral injections of OK432 induced OK432-reactive CD4+ T cells in the draining lymph nodes, and their in vitro production of interferon gamma was thus significantly enhanced by restimulation with OK432-pulsed DC. In addition, anti-P815 mastocytoma cytotoxic T lymphocytes were generated from the in vivo OK432-treated P815-draining lymph node cells only when the lymph node cells were restimulated in vitro with the DC pulsed with both P1A peptide and OK432. Moreover, the peritumoral injections of OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and P1A peptide, significantly suppressed the growth of s.c. inoculated P815. Interestingly, a significant level of IL-12 was detected in the coculture supernatant of both OK432-pulsed DC and OK432-reactive CD4+ T cells. Collectively, our results suggest that the antitumor vaccination effect of DC pulsed with class I tumor peptide could thus be effectively augmented by locally utilizing the Th1-type cytokines from OK432-reactive CD4+ T cells.

Animals↗

Characterization of B16 melanoma-specific cytotoxic T lymphocytes.

A B16 melanoma-specific CD8+ T cell line (AB1) was established from the spleen cells of C57BL/6 mice cured of B16 melanoma with interleukin (IL)-12 treatment. The AB1 line exclusively used T cell receptor Vbeta11. The AB1 cells exhibited a cytolytic activity against both syngeneic B16 melanoma and allogeneic P815 mastocytoma, whereas a cold inhibition assay revealed specificity of the AB1 cells against B16 melanoma. Their lostability to kill a class I loss variant of B16 melanoma was restored by the transfection of H-2Kb gene. In addition, their interferon (IFN)-gamma production was significantly suppressed by the addition of anti-H-2Kb monoclonal antibody, and RT-PCR analysis showed that the AB1 line expressed the mRNA encoding IFN-gamma, but not IL-4 or IL-10. The experiment using synthetic peptides of tyrosinase-related protein-2 (TRP-2) revealed that the AB1 cells could recognize TRP-2(181-188) peptide. Moreover, the AB1 cells showed an in vivo antitumor effect against established pulmonary metastases of B16 melanoma. Overall, these results indicate that the Tc1-type Vbeta11+ AB1 cells exert an antitumor activity against syngeneic B16 melanoma through recognition of TRP-2(181-188) peptide in an H-2Kb-restricted manner.

Animals↗

Involvement of both donor cytotoxic T lymphocytes and host NK1.1+ T cells in the thymic atrophy of mice suffering from acute graft-versus-host disease.

It has been reported that a dramatic decrease in the number of thymocytes (thymic atrophy) in mice suffering from acute graft-versus-host disease (GVHD) is ascribed to glucocorticoids. In this study, we examined the possibility that cellular immune responses may thus be involved in thymic atrophy. In contrast to chronic GVHD mice, acute GVHD (C57BL/6 X DBA/2) F1 (BDF1) hybrid mice, which were injected intravenously with both spleen and lymph node cells from C57BL/6 mice, showed a dramatic decrease in the number of CD4 CD8 double-positive thymocytes 2 or 3 weeks after the induction of GVHD. A flow cytometric analysis revealed the donor-derived T cells with either CD4 or CD8 molecules to infiltrate the thymus of the mice undergoing acute GVHD for 10 days. In a cytolytic assay, such thymus-containing cells exhibited a cytolytic activity specific to the host cells. In addition, anti-H-2d cytolytic T cells showed a high level of cytolytic activity against BDF1 (H-2bXd) thymocytes, whereas they also showed a low level of cytolytic activity against C57BL/6 (H-2b) thymocytes, thus suggesting that the thymus-infiltrating donor-derived T cells killed the host thymocytes through both anti-H-2d-specific and non-specific mechanisms. Interestingly, a flow cytometric analysis revealed both the percentage and the absolute cell number of host-derived NK1.1+ CD3+ cells to increase in the thymus of mice suffering from acute GVHD for 10 days. In addition, they also showed the cytolytic activity against YAC-1 cells and the mRNA expression of interleukin-12 (IL-12) in the thymus to be also significantly augmented on day 7 after the induction of acute GVHD. Collectively, our results indicate that the cellular immune responses such as donor cytotoxic T lymphocytes and host NK1.1+ T cells are therefore involved in the thymic atrophy of mice suffering from acute GVHD.

Acute Disease↗

Increased serum concentration of interleukin-5 in patients with Graves' disease and Hashimoto's thyroiditis.

We investigated serum levels of interleukin-5 (IL-5) in order to examine the role of T-helper 2 (Th2)-type immune response in the pathogenesis of autoimmune thyroid diseases. Serum levels of IL-5 were determined by a highly sensitive sandwich enzyme-linked immunosorbent assay in 42 patients with Graves' disease, 32 patients with Hashimoto's thyroiditis, 12 patients with silent thyroiditis, and 21 normal controls. Compared with serum levels in normal subjects (5.8 +/- 4.2 pg/mL), IL-5 was increased in patients with Graves' disease (16.4 +/- 16.7 pg/mL, p < .01), and in patients with Hashimoto's thyroiditis (10.0 +/- 7.6 pg/mL, p < .05), but not in patients with silent thyroiditis. There was no correlation between serum free thyroxine (FT4) and IL-5 levels. These data suggest an important role of the Th2-type immune response in the pathogenesis of Graves' disease and Hashimoto's thyroiditis.

Adult↗

Serum concentration of soluble Fas in patients with autoimmune thyroid diseases.

Fas is an apoptosis-signaling receptor molecule found on the surface of a number of cell types. Malfunction of the Fas system accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction. Soluble Fas (sFas) molecule lacks the transmembrane domain due to alternative splicing and blocks Fas-mediated apoptosis. This study investigated serum levels of sFas in autoimmune thyroid diseases. Serum levels of sFas were determined by enzyme-linked immunosorbent assay in 46 patients with Graves' disease, 32 patients with Hashimoto's thyroiditis, 14 patients with silent thyroiditis, and 24 normal controls. Compared with normal subjects (1.43+/-0.37 ng/mL), sFas was increased in thyrotoxic patients with Graves' disease (1.89+/-0.47 ng/mL, p < 0.001), and was decreased in patients with Graves' disease in remission (1.02+/-0.41 ng/mL, p < 0.001) and in euthyroid patients with Hashimoto's thyroiditis (0.97+/-0.25 ng/mL, p < 0.0001), but was normal in hypothyroid patients with Hashimoto's thyroiditis and in thyrotoxic patients with silent thyroiditis. Thus, changes in serum levels of sFas could not be explained by changes in serum thyroid hormones, although sFas concentration correlated with free thyroxine (r = 0.692, p < 0.0001). Also, the levels of sFas significantly correlated with the activities of TSH receptor antibody in Graves' disease (r = 0.671, p < 0.0001). Increased sFas in Graves' disease suggests increased expression of alternatively spliced Fas mRNA variant that produces sFas protein and decreased of cell surface expression of Fas, and may induce thyroid cell growth and production of TSH receptor antibody by protecting against apoptosis of thyroid cells and autoreactive B cells. Decreased sFas in Hashimoto's thyroiditis suggests decreased Fas mRNA variant and increased full-length Fas mRNA and membrane Fas, and may induce destruction of thyroid cells by promoting apoptosis of thyroid cells.

Adult↗

Low response of the thyroid gland to endogenous thyrotropin increased by thyrotropin-releasing hormone in patients with euthyroid Graves' disease.

Euthyroid Graves' disease is defined as Graves' ophthalmopathy without hyperthyroidism, and the thyroid-stimulating antibody (TSAb) has been known to be a good marker for diagnosis. However, the question of why TSAb does not cause hyperthyroidism arises. To settle this, we examined thyroid responsiveness to endogenous thyrotropin (TSH) increased by thyrotropin-releasing hormone (TRH) in 23 patients with euthyroid Graves' disease. Nineteen patients (83%) had positive TSAb and 21 (91%) had at least one of the autoantibodies to the thyroid gland. Only one patient (4%) had positive thyroid-stimulation blocking antibody (TSBAb). Basal levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin (TSH) in patients were not different from those in age- and sex-matched normal controls (n = 25). Response of TSH to TRH was normal; however, an increase of FT3, either absolute or as a multiple of baseline, in the TRH test in these patients (0.46+/-0.23 pg/mL, P < 0.001; 1.14+/-0.09 fold, p < 0.001) was significantly lower than that in controls (0.86+/-0.19 pg/ml; 1.26+/-0.07 fold). There was no correlation between the deltaFT3/deltaTSH ratio and TSAb activity. It is concluded that thyroid responsiveness in euthyroid Graves' disease is lower than in normal controls and this explains the euthyroid function in the patients even in the presence of TSAb.

Adolescent↗

Endoscopic retrograde cholangiopancreatography in paediatric patients with biliary disorders.

Endoscopic retrograde cholangiopancreatography (ERCP) has long been used in children. The usefulness of ERCP in paediatric patients with various biliary disorders, however, has not been well documented. Thirty-two sessions of ERCP performed in 29 paediatric patients ranging in age from 1 month to 15 years were evaluated. Endoscopic retrograde cholangiopancreatography was to confirm diagnosis or to obtain detailed information about their pancreaticobiliary system. Cannulation was successful in all patients. Opacification of the biliary tracts was also successful in all except for three patients with extrahepatic biliary atresia. Endoscopic retrograde cholangiopancreatography was assessed to be successful in making a differential diagnosis of neonatal hepatitis from extrahepatic biliary atresia, and in having a confirmed diagnosis of anomalous arrangement of the pancreaticobiliary ductal system associated with choledochal cyst. The procedure was also useful for obtaining detailed information on the pancreaticobiliary system in the other children. No accidents occurred during the endoscopic procedures in any of the paediatric patients. When a confirmed diagnosis or detailed information is needed in paediatric patients with biliary disorders, ERCP is a useful and safe technique.

Adolescent↗

Effectiveness of tonsillectomy in adult sleep apnea syndrome.

Tonsillectomy was performed on 10 adult sleep apnea patients (five males, five females; average age, 39 years old; average body mass index, 24.8 kg/m2). Tonsillectomy alone was indicated if tonsillar hypertrophy was moderate to severe and the length of the soft palate was less than 35 mm according to cephalometry. Remarkable improvements were observed in all cases following surgery. The average weight of the resected tonsils was 11 g. The patients demonstrated a preoperative apnea + hypopnea index (AHI) of 14.4/h. This decreased to 2.9/h postoperatively. The intraesophageal pressure change improved from -36.6 to -15.7 cmH2O following surgery. A significant correlation between preoperative AHI and the degree of obesity (r=0.684, P < 0.05) was found. Although uvulopalatopharyngoplasty has been used extensively to treat sleep apnea, the present results suggests that certain subjects can be effectively treated through only tonsillectomy.

Adult↗

Effectiveness of prosthetic mandibular advancement for obstructive sleep apnea: analysis by sleep position.

Fifteen patients with obstructive sleep apnea were treated using prosthetic mandibular advancement (PMA). Each patient was evaluated in the supine and lateral decubitus positions with and without PMA. After PMA treatment, the mean intraesophageal pressure (Peso) in the supine position improved from -42.6 to -27.3 cmH2O and the mean apnea + hypopnea index (AHI) decreased from 48.8/h to 23.7/h. The mean Peso in the lateral decubitus position improved from -27.9 to -18.6 cmH2O and the mean AHI decreased from 9.6/h to 6.6/h. With PMA, respiratory, disturbance during sleep further improved by changing the body position from the supine to lateral decubitus position.

Adult↗

Earlobe reconstruction using a subcutaneous island pedicle flap after resection of "earlobe keloid".

BACKGROUND: A large keloid of the earlobe is a difficult case in which to obtain a satisfying result by nonsurgical therapies. In this case, surgical resection of keloids should be considered as a first step in therapy. However, it is difficult to reconstruct the earlobe cosmetically after resection of the lesion. OBJECTIVE: To discuss the usefulness of the subcutaneous island pedicle flap in earlobe keloid surgery. METHODS: Five earlobe keloids in five patients (four females and one male) were resected and reconstructed by subcutaneous island pedicle flap. RESULTS: In all patients, there were no keloid recurrences and no adjuvant therapies used during the follow-up periods, which ranged from 10 to 26 months. The reconstructed earlobes were almost symmetrical. CONCLUSION: In the selected cases, use of the subcutaneous island pedicle flap is a viable method to be considered for reconstruction after resection of earlobe keloids.

Adult↗

Metastatic tumor thrombus attached to a pacemaker electrode.

We present a patient with a large tumor embolus attached to a pacemaker electrode leading to multiple pulmonary emboli. At postmortem examination, this thrombus was composed of clusters of well-differentiated squamous cell carcinoma intermingled with fibrin. Tumor involvement was not evident in the myocardium, endocardium, or epicardium. The primary tumor was discovered in the lower intrathoracic esophagus. Tumor microemboli from the esophageal primary lesions may have accumulated around the pacemaker electrode due to turbulent flow in this region, producing a large and friable tumor embolus.

Aged↗

Simple electrocardiographic criteria for identifying the site of origin of focal right atrial tachycardia.

UNLABELLED: To construct an algorithm for identifying the precise site of origin of focal right atrial tachycardia (RAT), we analyzed the P wave configuration in 32 patients with RAT who underwent successful radiofrequency catheter ablation. The RA was divided into three areas in the left anterior oblique view: superolateral, inferolateral, and inferomedial. There were 17 RATs arising from the crista terminalis (CT-AT), 12 from the tricuspid annulus (TA-AT), and 3 from the septum away from the TA (Sep-AT). A negative P wave in lead aVR identified CT-AT with a sensitivity (sens) of 100% and a specificity (spec) of 93%. In CT-ATs, positive P waves in the inferior leads differentiated superolateral AT from inferolateral AT with a sens of 86% and a spec of 100%. In any type of AT with inferomedial or inferolateral foci, the P wave deflections in at least one of the inferior leads was negative, and negative P waves in leads V5 and V6 identified inferomedial AT with a sens of 92% and a spec of 100%. In ATs near the apex of Koch's triangle, the P wave duration in the inferior leads was shorter than during sinus rhythm. CONCLUSIONS: (1) the P wave configuration in lead aVR can easily differentiate CT-AT from TA-AT and Sep-AT; (2) the P wave configuration in the inferior leads helps to determine a superior versus inferior origin in any type of AT; (3) in inferior AT, the P wave polarity in leads V5 and V6 is useful in determining a lateral versus medial origin; (4) this algorithm can predict accurately the origin of AT.

Algorithms↗

Retrograde Purkinje potential activation during sinus rhythm following catheter ablation of idiopathic left ventricular tachycardia.

We describe two patients with idiopathic left ventricular tachycardia that were cured by radiofrequency catheter ablation. Tachycardia was inducible by ventricular stimulation and was verapamil sensitive. Two distinct presystolic potentials (P1 and P2) were recorded during tachycardia in the mid-septal or inferoapical area, but only one potential (P2) was recorded during sinus rhythm. After catheter ablation at this site, the P1 potential was noted after the QRS complex during sinus rhythm, while the P2 was still observed before the QRS complex. The P1 potential showed a decremental property during atrial or ventricular pacing. These data suggest that Purkinje tissue with decremental properties was responsible for the tachycardia mechanism, and that the reentry circuit involving this tissue is likely to be of considerable size.

Anti-Arrhythmia Agents↗

Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients.

INTRODUCTION: Verapamil-sensitive left ventricular tachycardia (VT) with a right bundle branch block (RBBB) configuration and left-axis deviation has been demonstrated to arise from the left posterior fascicle, and can be cured by catheter ablation guided by Purkinje potentials. Verapamil-sensitive VT with an RBBB configuration and right-axis deviation is rare, and may originate in the left anterior fascicle. METHODS AND RESULTS: Six patients (five men and one woman, mean age 54+/-15 years) with a history of sustained VT with an RBBB configuration and right-axis deviation underwent electrophysiologic study and radiofrequency (RF) ablation. VT was slowed and terminated by intravenous administration of verapamil in all six patients. Left ventricular endocardial mapping during VT identified the earliest ventricular activation in the anterolateral wall of the left ventricle in all patients. RF current delivered to this site suppressed the VT in three patients (ablation at the VT exit). The fused Purkinje potential was recorded at that site, and preceded the QRS complex by 35, 30, and 20 msec, with pace mapping showing an optimal match between the paced rhythm and the clinical VT. In the remaining three patients, RF catheter ablation at the site of the earliest ventricular activation was unsuccessful. In these three patients, Purkinje potential was recorded in the diastolic phase during VT at the mid-anterior left ventricular septum. The Purkinje potential preceded the QRS during VT by 66, 56, and 63 msec, and catheter ablation at these sites was successful (ablation at the zone of slow conduction). During 19 to 46 months of follow-up (mean 32+/-9 months), one patient in the group of ablation at the VT exit had sustained VT with a left bundle branch block configuration and an inferior axis, and one patient in the group of ablation at the zone of slow conduction experienced typical idiopathic VT with an RBBB configuration and left-axis deviation. CONCLUSION: Verapamil-sensitive VT with an RBBB configuration and right-axis deviation originates close to the anterior fascicle. RF catheter ablation can be performed successfully from the VT exit site or the zone of slow conduction where the Purkinje potential was recorded in the diastolic phase.

Adult↗

Selected slow pathway ablation in a patient with corrected transposition of the great arteries and atrioventricular nodal reentrant tachycardia.

We report the first known case of AV nodal reentrant tachycardia (AVNRT) associated with a corrected transposition of the great arteries to be treated successfully by ablation of the slow pathway. Triple AV nodal pathways were observed in the anterograde direction and two types of AVNRT were induced. Input of the fast pathway to the AV node was located at the anterior portion of the left-sided AV annulus, while the input of the intermediate and slow pathways was located at the anteroseptal portion of the right-sided AV annulus. Radiofrequency energy ablation at the right anteroseptal site eliminated the intermediate and slow pathways.

Atrioventricular Node↗

Prediction of postpartum onset of rheumatoid arthritis.

OBJECTIVE: To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA). METHODS: Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were measured in early pregnancy by the antihuman IgG latex agglutination test (Latex test) and antirabbit IgG haemagglutination test (RAHA test). RESULTS: Latex test and RAHA test were positive in 26 (1.0%) and 64 (2.5%) pregnant subjects, respectively. Four hundred and ten subjects of 2547 pregnant women could be followed up for one year after delivery. None of 401 subjects without RF, or with only one RF on either Latex test or RAHA test, developed RA after delivery. Two (22.2%) of nine subjects with both RFs developed RA at one and three months postpartum, respectively. Transient arthralgia was found within 12 months postpartum in three of nine (33.3%) subjects with both RFs and this prevalence was significantly higher than that in RF negative subjects (8.1%). CONCLUSION: Postpartum onset of RA was found in at least 2 of 2547 healthy subjects (0.08%) and onset was predicted by positive test for rheumatoid factors.

Adult↗