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Biomedical subjects

S Miyamoto

Publications and source records attributed to S Miyamoto.

At least 73 records · Page 4Linked to original sources

Macroscopic typing with wall stricture sign may reflect tumor behaviors of advanced colorectal cancers.

No appropriate macroscopic classification of advanced colorectal cancers (A-CRC) is available for assessing their tumor behavior. In the present study, A-CRC were classified macroscopically as either stricture or nonstricture type, and the differences in clinicopathological features, mode of recurrence, and prognosis between the two types were investigated. The subjects were 166 patients with A-CRC invading beyond the muscular layer who had undergone curative surgical resection. Fresh resected specimens from these patients were used for the study. The A-CRC were classified as of stricture or nonstricture type according to whether or not they showed marked fold convergence and/or stricture of the intestinal tract (more than 30% wall shrinkage) that had the appearance of a "bow tie". Of the 166 A-CRC, 47 (28%) were classified as stricture type. This type was significantly more frequent in the colon (37%; 37/101) than in the rectum (15%; 10/65) (P = 0.003). The stricture type was more frequently associated with an abundance of fibrosis than the nonstricture type (76%; 28/37 vs 39%; 25/64 in colon; P < 0.001; 100%, 10/10 vs 42%, 23/55 in rectum; P < 0.001). The recurrence rate was also higher in the stricture type than in the non-stricture type in both the colon (51%, 19/37 vs 17%, 11/64; P = 0.003) and rectum (80%, 8/10 vs 38%, 21/55; P = 0.01). The time to recurrence was significantly shorter for the stricture type in both the colon (P < 0.001) and rectum (P = 0.02). These results indicate that the macroscopic typing of A-CRC according to the presence or absence of wall stricture sign may reflect their tumor behavior, although this behavior appears to be complex and related to tumor progression. This classification could be important clinically to assess tumor behavior in a simple way.

Aged↗

Ruptured aneurysm of the visceral artery: report of two cases.

We present herein two cases of a ruptured aneurysm of the visceral artery. The first case involved a 74-year-old man with abdominal pain who was admitted to our hospital with a tentative diagnosis of intra-abdominal bleeding of unknown origin. Computed tomography revealed a hematoma in the greater curvature of the stomach. At surgery, a hematoma along the right gastroepiploic artery was found and totally removed. Histological examination showed a pseudo-aneurysm of unknown etiology. The second case involved a 68-year-old man with progressive anemia who presented with spontaneous intra-abdominal bleeding. A ruptured aneurysm of the accessory middle colic artery was diagnosed by superior mesenteric angiography. The ruptured aneurysm was ligated and totally resected without a colectomy. Histological examination showed a pseudoaneurysm of unknown etiology. The postoperative courses were uneventful, and both patients were doing well at the time of writing.

Abdomen, Acute↗

Stented elephant trunk method for multiple thoracic aneurysms.

Stent-grafting and open graft replacement was introduced to reduce the complications of suture anastomosis in the descending aorta. We applied this technique in the treatment of a patient with multiple thoracic aneurysms. The elephant trunk procedure was used for thromboexclusion. A single branched graft was placed easily without twisting. In patients with aneurysms at both the proximal and distal thoracic aorta, combined stent-grafting and open graft replacement is an excellent approach.

Aged↗

Helical CT scanning of laryngeal deviation.

OBJECTIVE: To evaluate helical computed tomography (CT) scanning in patients with laryngeal deviation. MATERIALS AND METHODS: Five patients with laryngeal deviation and three control subjects underwent helical CT. The laryngeal deviation was idiopathic in one patient and acquired in four. Three-dimensional (3D) images of the laryngeal cartilages and bones, 3D airway surface models, and sequential coronal and axial images were reconstructed for assessment. RESULTS: The thyroid cartilage was inclined and twisted to the right in three patients, inclined to the right and twisted to the left in one patient, and inclined to the left and twisted to the right in one patient. The infero-posterior part of the thyroid cartilage, and the cricoid and arytenoid cartilages were shifted to the left in four patients. The vocal cords were at the level of C4 approximately C4/C5 in two patients, C4/C5 in one, C4/C5 approximately C5 in one, and C5 approximately C5/C6 in one. In four patients, inclination of the laryngeal cavity to the right may have induced left false vocal cord protrusion. The levels of the two false vocal cords differed in all patients. When the inclination and twisting were corrected on the computer, 3D images of the laryngeal cartilages of the patients became almost the same as those of the control subjects, except for slight deformity of the thyroid cartilage. The width of the right and left thyroid alae was measured on the computer, and was almost equal in all patients. 3D airway surface models of the left hemilarynx resembled those of the right hemilarynx when the angle of view was changed on the computer. CONCLUSION: Three-dimensional images of the laryngeal cartilages and bones, 3D airway surface models, and sequential coronal and axial CT scans were obtained using helical CT. This method allows the 3D observation of laryngeal deviation, and viewing of images from various directions on the computer was useful to understand the characteristics of laryngeal deviation.

Aged↗

Interaction between peroxisome proliferator-activated receptor gamma and its agonists: docking study of oximes having 5-benzyl-2,4-thiazolidinedione.

The molecular modelling of oximes having 5-benzyl-2,4-thiazolidinedione moieties, agonists of the peroxisome proliferator-activated receptor gamma (PPAR gamma), was performed with respect to their structures complexed with the ligand binding domain of PPAR gamma. For each ligand molecule, the 5-benzyl-2,4-thiazolidinedione head group was used as an anchor and the conformation of the rest of the molecule was searched for the most energetically favorable interaction with the receptor by systematic conformation search and manual modelling. Although both tail-up and tail-down configurations, which have been observed in the crystal structure of eicosapentaenoic acid when complexed with PPAR delta, appeared among the lowest energy structures for most of the compounds, potent agonists were found to adopt a configuration similar to that of rosiglitazone when bound to PPAR gamma, according to the crystal structure. The structure-activity relationships were analyzed based on the receptor-ligand interaction. The alkyl group and the aromatic ring of the tail group of the ligands had hydrophobic interactions with the receptor, and these interactions were found to be essential for the strong activity.

Hypoglycemic Agents↗

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT): initial aims and impact of the family history of type 1 diabetes mellitus in Japanese children.

The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes (JSGIT) was established in July 1994 with the chief aim to improve the quality of therapy for type 1 diabetes in children, an entity far less common in Japan than in Europe. We proposed four initial research topics: (i) to determine the current status of medical care and glycemic control in Japanese children with type 1 diabetes mellitus; (ii) to standardize the measurement of hemoglobin A1c; (iii) to establish a registry of a large cohort of patients in order to enable prospective studies to improve the quality of therapy for children with type 1 diabetes in Japan; and (iv) to enable participants of the JSGIT to hold a workshop twice annually. We registered a total of 736 patients from 45 hospitals throughout Japan. Intervention via insulin treatment was instituted after 2 yr for those patients whose hemoglobin A1c level was more than 8.1%. The proportion of patients receiving multiple insulin injections increased after intervention; however, average hemoglobin A1c in females remained significantly higher than in males. We identified two forms of diabetes in Japanese children: a rapidly progressive form and a more slowly progressive form. There was a significantly higher prevalence of a family history of diabetes in first-degree relatives in the slowly progressive form. These preliminary findings are the result of the first collaborative study of childhood diabetes in Japan.

Journal Article↗

Cytotoxic T lymphocyte antigen 4 gene polymorphism confers susceptibility to type 1 diabetes in Japanese children: analysis of association with HLA genotypes and autoantibodies.

OBJECTIVE: Although the polymorphisms of the cytotoxic T lymphocyte antigen 4 (CTLA4) gene have been shown to be associated with Type 1 diabetes in Caucasians, some conflicting results have been reported among subjects of different ethnic backgrounds. We examined a CTLA4 polymorphism and its relationship to human leucocyte antigen (HLA) genotypes and autoantibodies for glutamic acid decarboxylase 65 (GAD65) and IA-2 in Japanese children with Type 1 diabetes. SUBJECTS AND MEASUREMENTS: The study group consisted of 125 childhood-onset Japanese subjects (50 males, 75 females) with Type 1 diabetes. The CTLA4 A/G polymorphism at position 49 was analysed using a PCR-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DRB1 and DQB1 genotypes were defined by DNA analysis using PCR-sequence-specific oligonucleotide (PCR-SSO) probes. The GAD65 autoantibody (GAD65Ab) and IA-2 autoantibody (IA-2Ab) titres were measured using radioimmunoassay. RESULTS: The distribution of genotype frequencies differs between subjects with Type 1 diabetes (GG: 46%, AG: 50%, AA: 5%) and controls (GG: 39%, AG: 44%, AA: 17%) (P < 0.01). The frequency of the G allele is higher in the diabetes group than in the controls (P < 0.05). When the subjects were subdivided according to HLA genotype, the two major HLA high-risk groups, with DR9-DQ9 and DR4-DQ4, that are unique to Japanese populations showed no difference in their CTLA4 polymorphism frequencies. Although no association between the CTLA4 polymorphism and the prevalence of GAD65Ab was found, CTLA4 GG subjects that had been newly diagnosed (< 9 months) had significantly higher levels of autoantibodies than AG subjects (P < 0.01). The prevalence and titres of IA-2Ab were not associated with the CTLA4 polymorphism. CONCLUSIONS: The CTLA4 gene might confer a susceptibility to childhood-onset Type 1 diabetes in the Japanese population. The association between this CTLA4 polymorphism and the HLA genotype was similar for both major groups with HLA high-risk alleles. CTLA4 might contribute to the humoral immune response to GAD in newly diagnosed subjects.

Abatacept↗

Duodenal tuberculosis with a choledocho-duodenal fistula.

A 22-year-old man visited our hospital (National Cancer Center Hospital East) complaining of fatigue and anorexia. A laboratory investigation demonstrated a biochemical 'picture' of obstructive jaundice. An abdominal CT showed a low density mass in the retropancreatic area with multiple enlarged periportal lymph nodes. Upper gastrointestinal endoscopy revealed active ulceration on the dorsal wall of the descending part of the duodenum, and histopathology of the biopsy specimen revealed an ulcer with reactive inflammatory cell infiltration; no tumor cells were detected. The possibility of neoplasm had been ruled out by the use of CT and angiography. The jaundice recovered spontaneously and the abdominal mass gradually decreased in size. Endoscopic retrograde pancreatography showed no evidence of pancreatic disease; however, endoscopic retrograde cholangiography showed a choledocho-duodenal fistula. This patient showed hypersensitivity against the tuberculin skin test and Mycobacterium tuberculosis was successfully detected in gastric juice by using a polymerase chain reaction method and culture. Biopsy samples obtained from the duodenal ulcer at the second upper gastrointestinal endoscopy showed chronic inflammation with an epithelioid granuloma, suggesting tuberculosis. We thus diagnosed this case as a duodenal tuberculosis with a choledocho-duodenal fistula. To the best of our knowledge, there has been no report available of duodenal tuberculosis being the cause of a choledocho-duodenal fistula.

Adult↗

Demonstration of the reentrant circuit of verapamil-sensitive idiopathic left ventricular tachycardia: direct evidence for macroreentry as the underlying mechanism.

The exact reentrant circuit of verapamil-sensitive idiopathic left ventricular tachycardia (ILVT) remains unclear. This case report demonstrates the reentrant circuit of ILVT. A 20-pole electrode catheter was placed along the left posterior fascicle during electrophysiologic study. ILVT was reproducibly induced by programmed ventricular stimulation. During the tachycardia, sequential diastolic potentials bridging the entire diastolic period were observed in the recordings from the electrodes positioned from left ventricular mid-septum to inferoapical septum. The slow conduction zone appeared to be composed of a false tendon in this patient. Entrainment of the ILVT from the right ventricular outflow tract at a different pacing cycle length revealed that a dominant conduction delay occurred at the proximal site of the slow conduction zone. Entrainment studies from several sites on the left ventricular septum confirmed that these sites where sequential electrical activity was recorded were included within the reentrant circuit. However, the left posterior fascicle itself seemed to be a bystander. This report provides the direct evidence of macroreentry as the underlying mechanism of this ILVT, adjacent to the left posterior fascicle.

Adult↗

Venous congestion is a major cause of neurological deterioration in spinal arteriovenous malformations.

OBJECTIVE: Although venous congestion is considered to be a major cause of progressive myelopathy in patients with spinal dural arteriovenous fistulae (DAVFs), the neurological deterioration in patients with spinal intradural arteriovenous malformations (AVMs) has been attributed to hemorrhage or to vascular steal. To reexamine this theory, we analyzed our own cases of spinal vascular diseases. METHODS: In 24 patients with spinal vascular diseases, those who demonstrated progressive myelopathy with T2 hyperintensity in the spinal cord on magnetic resonance imaging (MRI) were diagnosed as patients with congestive myelopathy. We further examined the clinical courses, MRI findings, and reversibility of these cases. RESULTS: Venous congestion was judged to be a cause of neurological deterioration in 13 patients (7 DAVFs, 6 intradural AVMs). The T2 signals on these patients' MRI scans were located in the center and extended over several levels not corresponding to distribution of ischemia due to arterial steal. Of the patients who were diagnosed with congestive myelopathy, no differences between those with DAVFs and those with intradural AVMs were apparent in terms of clinical manifestations and reversibility. Eight (four DAVFs, four intradural AVMs) of 13 patients experienced neurological improvement after treatment. All patients with poor outcomes had intervals from onset of more than 3 years and showed contrast enhancement of the spinal cord on MRI studies. CONCLUSION: Spinal intradural AVMs as well as spinal DAVFs can be a cause of venous congestive myelopathy. Regardless of its etiology, congestive myelopathy is potentially reversible if properly diagnosed and treated.

Adult↗

Enhanced formation of fibrosis in a rabbit aneurysm by gelatin hydrogel incorporating basic fibroblast growth factor.

OBJECTIVE: This study was undertaken to analyze whether the controlled release of basic fibroblast growth factor (bFGF) can promote intrasaccular thrombosis in an experimental aneurysmal model. METHODS: Carotid aneurysms were constructed in 80 rabbits with venous pouches and treated by placing gelatin hydrogels into each aneurysm incorporating 0, 25, 50, or 100 microg of bFGF or incorporating 100 microg of bFGF with different water contents. In the controls, the venous pouches either were not treated or were treated with gauze alone. Gelatin hydrogel was used for the controlled release of bFGF into the aneurysms. The formation of fibrosis in the aneurysms was histologically viewed to assess the area occupied by the fibrous tissues at 3 and 6 weeks after the hydrogel application. The effect of the bFGF dose and water content on obliterating the aneurysm by the hydrogels incorporating bFGF was also investigated. RESULTS: Six weeks after the application of gelatin hydrogels with a water content of 95 wt% incorporating 100 microg of bFGF, the lateral pouch orifice was completely closed, obliterating the aneurysm at the level of tissue appearance, in contrast to hydrogels incorporating lower doses of bFGF and other control agents. The venous pouch aneurysm was histologically occupied with the newly formed fibrous tissue, and the fibrous tissue area and percentage of the aneurysmal lumen occupied by the fibrosis-gauze complex were significantly larger than those of other hydrogel applications (P < 0.05). The neointima tissue was homogeneously covered with a monolayer of Factor VIII-positive cells. The fact that there was no difference in the water content in the fibrosis formation induced by the bFGF-incorporated gelatin hydrogels indicated that the hydrogel biodegradability did not affect the obliteration of the aneurysm. CONCLUSION: Local controlled release of bFGF stimulated the formation of in vivo fibrosis, resulting in obliteration of the aneurysm. The long-term results of the fibrous organization remain speculative.

Animals↗

Detection of early gene expression changes during activation of human primary lymphocytes by in vitro synthesis of proteins from polysome-associated mRNAs.

The rapid increase in protein synthesis during the mitogenic stimulation of human peripheral blood lymphocyte is the result of global and specific translational control mechanisms. To study some of these mechanisms, we examined the in vitro translatability of mRNAs associated with the polyribosome fraction. Polyribosome fractions were isolated from lymphocytes after activation with ionomycin and the phorbol ester PMA. The associated PAmRNAs were translated in the presence of mRNA-depleted rabbit reticulocyte lysate and [(35)S]Met, and the protein products were analyzed by SDS--PAGE and autoradiography. There was little synthesis of protein from the PAmRNAs isolated from unactivated T cells, but the PAmRNAs isolated from activated T cells showed a rapid increase in translatability. Translation of the PAmRNAs was sensitive to edeine and m7GTP, suggesting their cap-dependent translation. With activation, the majority of proteins showed increasing in vitro translation, but two proteins, p72 and p33, were found to have increased synthesis within 30 min, which decreased in 1 h. Transcription inhibitors were used to ascertain if regulation of their expression was transcriptional or translational. To identify these proteins, we used biotinylated lysine during the in vitro translation reaction, and we extracted the biotinylated protein by using streptavidin magnetic beads. The protein product was analyzed by mass spectrometry. p33 was identified as a prohibitin-like protein (BAP37), but the identification of p72 was not found in the databases. The distinct up-regulation and down-regulation of their protein expression suggest their tightly controlled regulation during early T cell activation.

Animals↗

Phenotypic modulation of vascular smooth muscle cells: dissection of transcriptional regulatory mechanisms.

The smooth muscle myosin heavy chain (MHC) gene and its isoforms are excellent molecular markers that reflect smooth muscle phenotypes. The SMemb/Nonmuscle Myosin Heavy Chain B (NMHC-B) is a distinct MHC gene expressed predominantly in phenotypically modulated SMCs (synthetic-type SMC). To dissect the molecular mechanisms governing phenotypic modulation of SMCs, we analyzed the transcriptional regulatory mechanisms underlying expression of the SMemb gene. We previously reported two transcription factors, BTEB2/IKLF and Hex, which transactivate the SMemb gene promoter based on the transient reporter transfection assays. BTEB2/IKLF is a zinc finger transcription factor, whereas Hex is a homeobox protein. BTEB2/IKLF expression in SMCs is downregulated with vascular development in vivo but upregulated in cultured SMCs and in neointima in response to vascular injury after balloon angioplasty. BTEB2/IKLF and Hex activate not only the SMemb gene but also other genes activated in synthetic SMCs including plasminogen activator inhibitor-1 (PAI-1), iNOS, PDGF-A, Egr-1, and VEGF receptors. Mitogenic stimulation activates BTEB2/IKLF gene expression through MEK1 and Egr-1. Elevation of intracellular cAMP is also important in phenotypic modulation of SMCs, because the SMemb promoter is activated under cooperatively by cAMP-response element binding protein (CREB) and Hex.

Animals↗

Postrepression activation of NF-kappaB requires the amino-terminal nuclear export signal specific to IkappaBalpha.

One of the most prominent NF-kappaB target genes in mammalian cells is the gene encoding one of its inhibitor proteins, IkappaBalpha. The increased synthesis of IkappaBalpha leads to postinduction repression of nuclear NF-kappaB activity. However, it is unknown why IkappaBalpha, among multiple IkappaB family members, is involved in this process and what significance this feedback regulation has beyond terminating NF-kappaB activity. Herein, we report an important IkappaBalpha-specific function dictated by its amino-terminal nuclear export sequence (N-NES). The IkappaBalpha N-NES is necessary for the postinduction export of nuclear NF-kappaB, which is a critical event in reestablishing a permissive condition for NF-kappaB to be rapidly reactivated. We show that although IkappaBalpha and another IkappaB member, IkappaBbeta, can enter the nucleus and repress NF-kappaB DNA-binding activity during the postinduction phase, only IkappaBalpha allows the efficient export of nuclear NF-kappaB. Moreover, swapping the N-terminal region of IkappaBbeta for the corresponding IkappaBalpha sequence is sufficient for the IkappaB chimera protein to export NF-kappaB similarly to IkappaBalpha during the postinduction state. Our findings provide a mechanistic explanation of why IkappaBalpha but not other IkappaB members is crucial for postrepression activation of NF-kappaB. We propose that this IkappaBalpha-specific function is important for certain physiological and pathological conditions where NF-kappaB needs to be rapidly reactivated.

Active Transport, Cell Nucleus↗

Upregulation of iNOS by COX-2 in muscularis resident macrophage of rat intestine stimulated with LPS.

We investigated the effect of lipopolysaccharide (LPS) on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in muscularis resident macrophages of rat intestine in situ. When the tissue was incubated with LPS for 4 h, mRNA levels of iNOS and COX-2 were increased. The majority of iNOS and COX-2 proteins appeared to be localized to the dense network of muscularis resident macrophages immunoreactive to ED2. LPS treatment also increased the production of nitric oxide (NO), PGE(2), and PGI(2). The increased expression of iNOS mRNA by LPS was suppressed by indomethacin but not by N(G)-monomethyl-L-arginine (L-NMMA). The increased expression of COX-2 mRNA by LPS was affected neither by indomethacin nor by L-NMMA. Muscle contractility stimulated by 3 microM carbachol was significantly inhibited in the LPS-treated muscle, which was restored by treatment of the tissue with L-NMMA, aminoguanidine, indomethacin, or NS-398. Together, these findings show that LPS increases iNOS expression and stimulates NO production in muscularis resident macrophages to inhibit smooth muscle contraction. LPS-induced iNOS gene expression may be mediated by autocrine regulation of PGs through the induction of COX-2 gene expression.

Animals↗

Glutathione attenuates coronary constriction to acetylcholine in patients with coronary spastic angina.

This study examined the effect of reduced glutathione (GSH), an important antioxidant that restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spastic coronary arteries. The responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh; 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50 mg/min for 6 min) or saline as a placebo in 24 patients with coronary spastic angina and in 28 control patients. All of the spastic coronary arteries showed constrictor response to ACh, whereas the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with coronary spastic angina, whereas it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated the constrictor response to ACh in epicardial coronary arteries of patients with coronary spastic angina. GSH may have an important role in the regulation of coronary vasomotor function in patients with coronary spastic angina.

Acetylcholine↗