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Biomedical subjects

T Ueyama

Publications and source records attributed to T Ueyama.

At least 73 records · Page 4Linked to original sources

Novel alternative splicing in the 5' exon of the neurotrophin-3 gene.

The neurotrophin-3 (NT-3) gene has previously been reported to consist of three exons including two 5' short untranslated exons and a 3' long exon encoding the entire protein, and to give rise to two classes of transcripts by alternative splicing of the 5' exons to the 3' coding exon. In the present study, we demonstrated the presence of at least four new classes of transcripts of the NT-3 gene, in addition to the two known transcripts. The present finding proposes the further complexity of the regulational mechanism for NT-3 expression.

Alternative Splicing↗

Transcription factor RTEF-1 mediates alpha1-adrenergic reactivation of the fetal gene program in cardiac myocytes.

Alpha1-adrenergic receptor stimulation induces cardiac myocytes to hypertrophy and reactivates many fetal genes, including beta-myosin heavy chain (betaMyHC) and skeletal alpha-actin (SKA), by signaling through myocyte-specific CAT (M-CAT) cis elements, binding sites of the transcriptional enhancer factor-1 (TEF-1) family of transcription factors. To examine functional differences between TEF-1 and related to TEF-1 (RTEF-1) in alpha1-adrenergic reactivation of the fetal program, expression constructs were cotransfected with betaMyHC and SKA promoter/reporter constructs in neonatal rat cardiac myocytes. TEF-I overexpression tended to transactivate a minimal betaMyHC promoter but significantly interfered with a minimal SKA promoter. In contrast, RTEF-1 transactivated both the minimal betaMyHC and SKA promoters. TEF-1 and RTEF-I also affected the alpha1-adrenergic response of the betaMyHC and SKA promoters differently. TEF-1 had no effect. In contrast, RTEF-1 potentiated the alpha1-adrenergic responses of the SKA promoter and of a -3.3-kb betaMyHC promoter. To determine why the promoters responded differently to TEF-1 and RTEF-1, promoters with mutated M-CAT elements were tested in the same way. The betaMyHC promoter required an intact M-CAT element to respond to TEF-1 and RTEF-1, whereas the SKA promoter M-CAT was required for the TEF-1 response but not for the RTEF-1 response, suggesting that SKA promoter-specific cofactors may be involved. By competition gel shift assay, the M-CAT of the minimal betaMyHC promoter had a lower affinity than that of the SKA promoter, which partly explains the different responses of these promoters to TEF-1. These results highlight functional differences between TEF-1 and RTEF-1 and suggest a novel function of RTEF-1 in mediating the alpha1-adrenergic response in hypertrophic cardiac myocytes.

Actins↗

Gene expression of neurotrophins and their receptors in cultured rat vascular smooth muscle cells.

Most previous researches on neurotrophins including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) have focused on the nervous system, because their receptors are widely distributed in neuronal tissues. Recently, however, the participation of neurotrophins in inflammation and atherosclerosis has been proposed. Therefore, the gene expression of neurotrophins is now an urgent issue is to be investigated in nonneuronal tissues. Here, we evaluated the gene expression of neurotrophins and their receptors in rat cultured vascular smooth muscle cells (VSMCs) by the reverse transcriptase-polymerase chain reaction method. The transcripts of NGF, NT-3, and TrkC (high-affinity receptor for NT-3), and two BDNF alternative spliced transcript variants with exons 3 and 4 were clearly detected in VSMCs cultured under conventional culture conditions. The upregulation of mRNA levels for NGF, two BDNF variants with exons 1 and 2, low-affinity neurotrophin receptor, and high-affinity receptors, TrkA (for NGF) and TrkB (for BDNF), was observed in response to the treatment with serum and phorbol-ester following the serum-starvation. In contrast, the expression of NT-3 and TrkC genes was downregulated under these conditions. Co-expression of these factors and their receptors and the characteristic regulation of their gene transcriptions suggest that these factors play crucial roles in the function of VSMCs through an autocrine mechanism.

Alternative Splicing↗

Natural history of colorectal carcinoma: can the tumor volume doubling time be predicted by radiologic findings or immunohistochemical variables?

BACKGROUND AND OBJECTIVES: The factors influencing the growth rate of colorectal carcinoma have not been determined. The aim of this study was to clarify the relationship between the doubling time (DT), morphology, and proliferating cell nuclear antigen, Ki-67 and p53 immunohistochemistry in colorectal carcinoma. METHODS: Thirty-three patients (37 lesions) were studied retrospectively. The DT was calculated and correlated with the initial and final tumor size, morphologic shape, and immunohistochemical results. RESULTS: The DT ranged from 2.4 to 48.0 months (mean: 12.0 months). The mean DT of the early-stage carcinomas was significantly longer than that of the advanced carcinomas. In the latter group, both slowly growing and rapidly growing tumors were observed. The DT showed no correlation with the initial or final size and shape of the tumors on radiographs, or with the immunohistochemical results. CONCLUSIONS: Our data revealed that it is not possible to evaluate the growth rate of colorectal carcinomas based on their morphological shape, cellular proliferative activity, or tumor suppressor gene activity.

Adenocarcinoma↗

Transforming growth factor-beta1 and protein kinase C synergistically activate the c-fos serum response element in myocardial cells.

We previously reported that transforming growth factor-beta1 (TGF-beta1) potentiated alpha1-adrenergic and stretch-induced c-fos mRNA expression and norepinephrine (NE)-induced amino acid incorporation in rat cultured myocardial cells (MCs). In the present study, we attempted to explore the mode of TGF-beta1 action for c-fos gene expression in MCs. In the transient transfection assay, TGF-beta1 potentiated NE- or 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated c-fos promoter/enhancer, but not forskolin-activated c-fos promoter/enhancer. The c-fos serum response element (SRE) and the TPA response element (TRE) were responsible for TGF-beta1-induced potentiation of the NE or TPA action. Although TGF-beta1 activated not only the wild-type c-fos SRE, but also the mutated c-fos SRE, which contains an intact binding site for the serum response factor (SRF) but lacks the ternary complex factor (TCF) binding site, TPA activated the wild-type c-fos SRE but not the mutated c-fos SRE. TGF-beta1 did not potentiate the effects of TPA on the activation of mitogen-activated protein kinase (MAPK) and the phosphorylation of Elk-1 and SAP-1a, which belong to TCF at the c-fos SRE. These results indicate that TGF-betaf potentiates the c-fos SRE activated by PKC through the SRF binding site. TGF-beta1 is involved in the regulation of c-fos gene expression through the c-fos SRE and is subsequently involved in the regulation of the gene which has the TRE in the promoter/enhancer region.

Animals↗

[Removal of infected pacemaker lead through sternotomy without cardiopulmonary bypass].

A 66-year-old man, who had undergone DDD pacemaker implantation for complete A-V block two years ago, was admitted because of endocarditis with septicemia and renal failure. His blood culture revealed Staphylococcus aureus. We tried to remove the infected cardiac pacemaker lead. But we failed to remove the atrial lead because it was strongly adhered with the right atrial appendage. Antibiotic therapy was ineffective. In the last resort, we operated through median sternotomy three months after the initial infectious episode. In intraoperative inspection, we found it difficult to remove the lead by traction because of atrial residual lead sticking out of the right atrial appendage. We applied a purse string suture on the right appendage and obtained successful removal of infected lead without the cardiopulmonary bypass. His postoperative course has been uneventful. He is totally asymptomatic and doing well up to now. In case of such local infection, we conclude that all transvenous leads should be removed and recommend a simultaneous implantation of the epicardial pacemaker system.

Aged↗

Growth hormone preserves cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors) and enhances cardiac function in cardiomyopathic hamsters.

OBJECTIVE: Growth hormone (GH) improves cardiac function in experimental models of heart failure and human dilated cardiomyopathy. However, the mechanism by which GH increases myocardial contractility is not entirely clear. Our aim was to examine the effects of GH on cardiac function and cardiac sarcoplasmic reticulum Ca2+ release channels (ryanodine receptors, RyR) in the hearts of UM-X7.1 cardiomyopathic hamsters during the development of heart failure. METHODS: Experimental and healthy control hamsters were examined at the age of 20 weeks. Recombinant human GH (2 mg/kg/day, s.c.) or vehicle was then administered for 3 weeks. We examined (i) the in vivo left ventricular (LV) size and LV systolic function using transthoracic echocardiography, (ii) the density (Bmax) and affinity (Kd) of high-affinity [3H] ryanodine binding sites in crude homogenates from normal and cardiomyopathic hamster hearts. RESULTS: Vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular end-diastolic diameter and end-systolic diameter (LVESd), and a significant decrease in LV fractional shortening (FS). GH-treatment attenuated the increase in LVESd and reduced the LV chamber size, and also significantly increased LVFS. Vehicle-treated UM-X7.1 hamsters exhibited a significantly lower Bmax than control hamsters (0.34 +/- 0.04 vs 0.44 +/- 0.06 pmol/mg, p < 0.05), and the treatment with GH in UM-X7.1 hamsters significantly attenuated the reduction of Bmax (0.42 +/- 0.03 pmol/mg vs vehicle-treated group (0.34 +/- 0.04 pmol/mg), p < 0.05). Kd did not differ significantly between the experimental groups. In normal control hamsters, GH treatment with this dose did not significantly enhance LV systolic function or the density of RyRs. There was no significant difference in terms of the connective-tissue volume-fraction, myocyte size and capillary density between the GH- and vehicle-treated groups of UM-X7.1 hamsters. CONCLUSIONS: GH treatment may improve cardiac function by preserving the density of RyRs and enhancing cellular function in cardiomyopathic hamster hearts.

Animals↗

Large and invasive silent corticotroph-cell adenoma with elevated serum ACTH: a case report.

BACKGROUND: A silent corticotroph-cell adenoma (SCCA) is defined as evidence of immunoreactive ACTH in tumor cells of a pituitary adenoma that is not associated with symptoms of Cushing's disease. Most previous reports have discussed the etiology of this unique entity; however, the precise mechanisms of its "silence" are not clear yet. We discuss the pitfalls of endocrinological diagnosis and surgical management of SCCA. METHODS: A 63-year-old man, without the symptoms of Cushing's disease, demonstrated elevated serum levels of ACTH, but normal levels of cortisol. ACTH was measured by newly developed immunoradiometric assays (RMA), which are more specific for biologically active ACTH than conventional radioimmunoassay (RIA). The tumor was more than 3 cm in diameter and invaded both the cavernous sinus and the sphenoid sinus. RESULTS: Two different types of IRMAs revealed elevated serum ACTH levels. The tumor was removed successfully by staged operations. The high levels of serum ACTH were normalized after the second operation. CONCLUSION: The cause of the silence of SCCA is not clear yet. The elevated serum ACTH levels in the present case were not attributable to "Big ACTH." We suggest one possibility: the cause of the silence might be a minor variant of ACTH, detected by IRMA, leading to less biological activity of ACTH. This type of adenoma is invasive in nature and can potentially grow large because it is free of endocrinological symptoms. We emphasize the appropriate surgical strategy to normalize the serum levels of ACTH in case of SCCA.

Adenoma↗

Advance in the diagnosis of esophageal carcinoma. A new imaging process by adaptive spatial filtering of computed esophagograms.

PURPOSE: To assess the clinical utility of computed radiographic images processed with adaptive spatial filtering (ASF) in the diagnosis of esophageal carcinoma. MATERIAL AND METHODS: After determining the optimal values for ASF image parameters in double-contrast barium studies, we used ASF to process the esophagograms of 35 patients with 37 esophageal carcinomas (superficial 20, advanced 17). The image quality of each lesion was evaluated independently by four radiologists on the basis of detectability, extent, and surface structure. The scoring was: 1 when the ASF image was superior to the original; -1 when the converse was true; and 0 when quality of images was equal. RESULTS: In superficial carcinoma, the mean scores for image quality with regard to detectability, extent, and surface structure were 0.19, 0.48, and 0.31 respectively. In advanced carcinoma, the scores were 0.00, 0.76, and 0.25 respectively. CONCLUSION: ASF offers an improved image quality which is valuable in the evaluation of esophageal carcinoma, particularly in the detection of superficial carcinomas and in the identification of intraepithelial extension.

Barium Sulfate↗

Early esophageal carcinoma. Evaluation of the depth of invasion based on double-contrast esophagography.

PURPOSE: The aim of this study was to assess the depth of invasion of early esophageal carcinoma (EEC) by means of double-contrast esophagography. MATERIAL AND METHODS: The radiological findings of 46 EECs were retrospectively analyzed for the following factors that might be related to the depth of invasion: in depressed lesions (n = 30): maximum size, surface appearance, sharpness of contour, and wall rigidity; and in elevated lesions (n = 16): maximum size, height, shape, and wall rigidity. All lesions were surgically or endoscopically resected and the radiological findings were compared with the histological appearance. RESULTS: In depressed lesions, the size of the surface granules correlated very strongly with the depth of invasion (rs = 0.8147). In both depressed and elevated lesions, wall rigidity correlated strongly with the depth of invasion (rs = 0.7540 and rs = 0.6702 respectively). In depressed lesions, sharpness of contour also correlated strongly with the depth of invasion (rs = 0.6731). The other factors did not correlate with the depth of invasion. CONCLUSION: Double-contrast esophagography could provide useful information for assessing the depth of invasion of EECs.

Barium Sulfate↗

Effects of dantrolene sodium on progression of left ventricular hypertrophy induced by pressure overload in rats.

We studied the long-term effects of dantrolene sodium (D), a specific sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left ventricular pressure-overloaded hypertrophy in rats. We treated abdominal aorta-constricted rats with one of two doses of D for 4 weeks. The extent of hypertrophy was expressed as the ratio of left ventricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to normal levels, the progression of cardiac hypertrophy was not inhibited. In contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and inhibited the progression of cardiac hypertrophy. Dantrolene sodium had no effect on cardiac function in sham-operated rats. Thus control of Ca2+ release from the SR might be crucial in regulating the progression of cardiac hypertrophy, the final mediator possibly being intracellular Ca2+ concentration.

Animals↗

Polylysine-induced rapid Ca2+ release from cardiac sarcoplasmic reticulum.

The rapid kinetics of polylysine-induced Ca2+ release from cardiac sarcoplasmic reticulum (SR) was assessed in combination with its effect on ryanodine binding. SR vesicles were isolated from canine cardiac SR. The time course of SR Ca2+ release was continuously monitored by a stopped-flow apparatus, and [3H]ryanodine binding was done by using the filtration method. The initial rate of polylysine-induced Ca2+ release from cardiac SR revealed different concentration dependence from those observed in skeletal SR. The initial rate peaked at 0.11 microM, followed by a decrease at higher concentrations in skeletal SR, whereas it increased to 3.7 microM in cardiac SR. The [3H]ryanodine binding was also stimulated by polylysine with an identical parallelism with Ca2+ release in terms of polylysine concentration dependence. Thus we demonstrated that the cardiac SR Ca2+ release channel is sensitive to activation by polylysine and that there is a difference in the concentration dependence of polylysine-induced activation of cardiac and skeletal SR Ca2+ release channels.

Animals↗

Bridging veins on the tentorial surface of the cerebellum: a microsurgical anatomic study and operative considerations.

OBJECTIVE: When using the median infratentorial supracerebellar approach, all or numerous bridging veins over the cerebellar surface must be sacrificed. Such sacrifice potentially causes cerebellar venous infarction, especially when excessive cerebellar retraction is applied. To prevent such potential complications, neurosurgeons must have adequate knowledge of the anatomy of the bridging veins, particularly the hemispheric bridging veins. METHODS: In 14 cadaveric specimens (26 sides), the number, locations, and tributaries of both the vermian and hemispheric bridging veins between the superior surface of the cerebellum and the tentorium were examined with the aid of an operating microscope. In addition, particular attention was given to the distribution patterns and collateral pathways of the hemispheric bridging veins. RESULTS: The average number of vermian bridging veins per cerebellum was 3.24. The average number of hemispheric bridging veins per side was 1.69, and they were most frequently located in the intermediate third of the hemisphere (59.0%). The distribution patterns of the hemispheric bridging veins were classified into six groups according to the draining patterns of each cerebellar hemisphere. Each hemispheric bridging vein usually had several collateral pathways between other draining veins. The most prominent collateral pathways of the hemispheric bridging veins frequently connected with the vermian bridging veins. CONCLUSION: Anatomic familiarity with the bridging veins can minimize their intraoperative sacrifice and avert subsequent postoperative complications. This knowledge also assists in planning the best approach to the pineal region.

Cerebellum↗

Water immersion-restraint stress induces expression of immediate-early genes in gastrointestinal tract of rats.

The aims of this study were to determine 1) which cells are involved in stress-induced acute gastric mucosal lesion and 2) what kinds of molecular alterations are induced by stress, using immediate-early genes (IEG) as tools for detection of cellular activation. Male Wistar rats were exposed to acute water immersion-restraint stress. Protein and mRNA for IEG were detected by immunohistochemistry and in situ hybridization, respectively. This stress induced the expression of c-fos and nerve growth factor-induced gene (NGFI-A) mRNA in gastric epithelial cells, the smooth muscle layer of small blood vessels, and the stomach wall. Stress upregulated the mRNA levels of these IEG in the duodenal epithelial cells and induced de novo expression of IEG in the smooth muscle layer of small blood vessels and the duodenal wall. These findings indicate that these cells are activated in response to stress. Expression of these IEG and/or transcriptional factors may reflect an initiation of mechanisms for repairing the lesions induced by stress as well as an adaptation to the stress.

Animals↗

Alterations in cardiac SR Ca(2+)-release channels during development of heart failure in cardiomyopathic hamsters.

The cardiomyopathic Syrian hamster develops a progressive cardiomyopathy characterized by cellular necrosis, hypertrophy, cardiac dilatation, and congestive heart failure. This study aimed to identify alterations in cardiac mechanical function and in the cellular content of sarcoplasmic reticulum (SR) Ca(2+)-release channels (ryanodine receptors, RyR) in the heart of the UM-X7.1 cardiomyopathic hamster during the development of heart failure. Experimental and healthy control hamsters were examined at 8, 18, and 28 wk of age. The UM-X7.1 hamsters had developed left ventricular (LV) hypertrophy at 8 wk and a marked LV dilatation at 18-28 wk. During the latter stage, the UM-X7.1 hamster hearts showed global hypokinesis. Equilibrium binding assays of high-affinity sites for [3H]ryanodine were performed in ventricular homogenate preparations. There was no significant difference between the two groups in the maximum number of [3H]ryanodine binding sites (Bmax) at either 8 or 18 wk of age, although the cardiac pump function was impaired in UM-X7.1 hamsters at 18 wk of age. By 28 wk, Bmax was significantly lower in the UM-X7.1 hamsters. Quantitative immunoblot assay revealed that the content of RyR protein in cardiomyopathic hearts, which was increased at the early stage, declined to below normal as heart failure advanced. These results suggest that the number of RyR in the UM-X7.1 cardiomyopathic hamsters was preserved at both the hypertrophic and early stages of heart failure with a possibly compensatory increase in the level of protein expression, although the cardiac function already showed a tendency to be impaired.

Aging↗

Histologic characterization of gonadal stromal tumors induced by intrasplenic autografting of testicular tissue.

Intrasplenic heterotransplantation of infantile testis is a conventional method to produce testicular tumors in adult castrated rodents. To avoid possible immunological interferences in the tumorigenic process in the allografted testis, the testicular tissues were autografted into the spleen of 88 castrated Wistar strain rats. Intrasplenic tumors developed in 64 animals (73% incidence) during an experimental period of 24 months, and 91% of these were histologically categorized as gonadal stromal tumors including Sertoli cell tumors, Leydig cell tumors, mixed forms of these and granulosa cell tumors. Although radioimmunoassay revealed elevated levels of serum sex-steroid hormones in 19 tumor-bearing rats, the levels of the serum gonadotropins were not increased. The results indicate that the intrasplenic testicular cells can develop into both Sertoli and granulosa type tumors. Intrasplenic autografting is a feasible and reproducible method to induce testicular gonadal stromal tumors with a high incidence, and thus deserves further attention.

Animals↗

[Radiofrequency catheter ablation therapy in elderly patients with supraventricular tachycardia].

138 patients with Wolf-Parkinson-White (WPW) syndrome (n = 96), atrioventricular nodal reentrant tachycardia (AVNRT; n = 27) and the other supraventricular tachycardia (n = 15), were divided into two groups, a control group (less than 65 years old; n = 108) and an elderly group (more than 66 years old; n = 30). We then estimated the success rate and safety of radiofrequency ablation for supraventricular tachycardia in elderly patients. For WPW syndrome, there were 76 (97%) successes and 9 (13%) recurrences in the control group (n = 78). In the elderly group of WPW patients, the number of successes was 18 (100%) and the number of recurrences one (63%). In 27 patients with AVNRT, the number of successes was 26 (96%) and there were no recurrences. In 15 patients with some other supraventricular tachycardia, there were 11 patients (73%) successes and one recurrence (11%). Major complications consisted of cardiac tamponade in 2 patients, dissecting aneurysm in one patient and cerebral embolism in one patients. All major complications occurred in patients with WPW syndrome. The cause of the complications, except the cerebral embolism was manipulation of the electrical or ablation catheter. Three of four patients with major complications belonged to the control group. It is possible that radiofrequency catheter ablation for supraventricular tachycardia in elderly patients is safe and highly effective. However, it is still invasive therapy. Ablation on a left accessory pathway by the transaortic valve approach especially needs meticulous care.

Aged↗

[Surgical technique of endoscopic transthoracic sympathicotomy: axillary approach].

A total of 181 endoscopic transthoracic sympathicotomy were performed at our hospital from December, 1992 to March, 1997. After single-lumen endotracheal intubation for general anesthesia, the patient was placed in half sitting position. A small (1 cm) incision was made in the anterior axillary line through the third intercostal space and an apical pneumothorax was created by insufflation of 1.8 L of CO2 in the pleural cavity through a Surgineedle. A 24 Fr. urological transurethral electroresectoscope was introduced through the same incision. The sympathetic chain could be observed through parietal pleura riding on the costovertebral junctions. In palmar hyperhidrosis the second and third thoracic sympathetic ganglia were electrocoagulated. In axillary hyperhidrosis the forth ganglion was included. The lung was expanded by limiting expiration and sucking CO2. The operation was repeated on the other side. Endoscopic transthoracic sympathicotomy was an efficient, safe and low invasive surgical procedure for the treatment of palmar, axillary hyperhidrosis, Raynaud's disease and Buerger disease.

Axilla↗