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Biomedical subjects

K Suda

Publications and source records attributed to K Suda.

At least 19 recordsLinked to original sources

Spin correlations of strongly interacting massive fermion pairs as a test of Bell's inequality.

We report the results of the first-time test of the local hidden variable theories (Bell-Clauser-Horne-Shimony-Holt) involving strongly interacting pairs of massive spin 1/2 hadrons from the decay of short-lived (tau<10;-21sec) 2He spin-singlet state, populated in the nuclear reaction 2H+;1H-->;2He+n. The novel features of this experiment are (a) the use of an 'event-ready' [corrected] detector of nearly 100% efficiency to prepare an unbiased sample and (b) a focal-plane polarimeter of full 2pi sr acceptance with a random "post selection" of the reference axes. The spin-correlation function is deduced to be S[exp](pi/4)=2.83+/-0.24stat+/-0.07sys. This result is in agreement with nonlocal quantum mechanical prediction and it violates the Bell-CHSH inequality of |S|<or=2 at a confidence level of 99.3%.

Journal Article↗

Serum concentrations of high-mobility group box chromosomal protein 1 before and after exposure to the surgical stress of thoracic esophagectomy: a predictor of clinical course after surgery?

High-mobility group box chromosomal protein 1 (HMGB-1) has recently been shown as an important late mediator of endotoxin shock, intra-abdominal sepsis, and acute lung injury. However, its role in the systemic inflammatory response syndrome after major surgical stress, which may lead to multiple organ dysfunction syndrome, has not been thoroughly investigated. We hypothesized that serum HMGB-1 participates in the pathogenesis of postoperative organ system dysfunction after exposure to major surgical stress. A prospective clinical study was performed to consecutive patients (n = 24) with carcinoma of the thoracic esophagus who underwent transthoracic esophagectomy with three field lymph node resection between 1998 and 2003 at Keio University Hospital, Japan. Serum HMGB-1 concentrations were measured by enzyme-linked immunosorbent assay. Preoperative serum HMGB-1 levels correlated with postoperative duration of SIRS, mechanical ventilation, and intensive care unit stay. Three of the 24 patients had serious postoperative complications: sepsis in two, and acute lung injury in one. Serum HMGB-1 levels in patients without complications increased within the first 24 h postoperatively, remained high during postoperative days 2-3, and then decreased gradually by postoperative day 7. In patients with serious complications, serum HMGB-1 was significantly higher than that found in patients without postoperative complications at every time point except postoperative day 2. Preoperative serum HMGB-1 concentration seems to be an important predictor of the postoperative clinical course. Transthoracic esophagectomy induces an increase in HMGB-1 in serum even in patients without complications. Postoperative serum HMGB-1 concentrations were higher in patients who developed complications, and may be a predictive marker for complications in this setting.

Enzyme-Linked Immunosorbent Assay↗

Resolving the discrepancy of 135 MeV pd elastic scattering cross sections and relativistic effects.

Three precise measurements for elastic pd scattering at 135 MeV/A have been performed with the three different experimental setups. The cross sections are described well by the theoretical predictions based on modern nucleon-nucleon forces combined with three-nucleon forces. Relativistic Faddeev calculations show that relativistic effects are restricted to backward angles. This result supports the two measurements recently reported by RIKEN and contradicts the KVI data.

Journal Article↗

COX-2+ myofibroblasts may play a key role in marked stromal fibrosis in strictured colorectal carcinomas.

AIMS: To elucidate the mechanism of marked stromal fibrosis in strictured colorectal carcinomas (SC) that cause complete ileus. METHODS AND RESULTS: Sixteen cases of SC and 29 cases of non-strictured colorectal carcinoma (NSC) were studied. These carcinomas showed similar clinicopathological features except for bowel stricture. The stricture index (SI) showing the degree of bowel stricture was 59.8 +/- 12.1% in SC versus 20.8 +/- 24.6% in NSC (P < 0.001). The fibrosis index (FI), defined to reflect the extent of stromal fibrosis, was 56.3 +/- 8.8% in SC versus 21.9 +/- 10.6% in NSC (P < 0.001). COX-2+ myofibroblasts were detected in 13 cases (81.3%) in SC versus eight cases (27.6%) in NSC (P < 0.01). The COX-2+ myofibroblast density was 276.7 +/- 181.1 cells/mm(2) in SC versus 26.6 +/- 52.7 cells/mm(2) in NSC (P < 0.001). When all cases were divided into two groups with and without COX-2+ myofibroblasts, the SI was 48.8 +/- 19.1% in those with COX-2+ myofibroblasts versus 24.8 +/- 29.3% in those with COX-2- myofibroblasts (P < 0.001). CONCLUSION: COX-2+ myofibroblasts may play an important role in extensive bowel stricture in colorectal carcinomas.

Colonoscopy↗

Membrane protein reconstitution and crystallization by controlled dilution.

Efficient reconstitution of membrane proteins for functional analyses can be achieved by dilution of a ternary mixture containing proteins, lipids and detergents. Once the dilution reaches the point where the free detergent concentration would become lower than the critical micellar concentration, detergent is recruited from the bound detergent pool, and association of proteins and lipids is initiated. Here we show that dilution is also suitable for the assembly of two-dimensional crystals. A device has been designed that allows controlled dilution of a protein-lipid-detergent mixture to induce formation of densely packed or crystalline proteoliposomes. Turbidity is used to monitor the progress of reconstitution on-line, while dilution is achieved by computer-controlled addition of buffer solution in sub-microliter steps. This system has mainly been tested with porin OmpF, a typical beta-barrel protein, and aquaporin-1, a typical alpha-helical protein. The results demonstrate that large, highly ordered two-dimensional crystals can be produced by the dilution method.

Aquaporin 1↗

Echocardiographic evaluation of fetal hydrothorax: the effusion ratio as a diagnostic tool.

OBJECTIVE: Fetal hydrothorax may lead to hydrops and is associated with mortality as high as 50%. The objective of this study was to define the pathophysiology of fetal hydrothorax and its relation to hydrops. METHODS: Measurements from echocardiograms of 33 fetuses diagnosed with hydrothorax were made, and included diameters of the thorax, heart, inferior vena cava, right ventricle (RV), left ventricle (LV) and aortic and pulmonary valves. Doppler-derived velocities were measured in the aorta and pulmonary artery just above the aortic and pulmonary valves. The ratio of the area of the effusion to the area of the thorax (effusion ratio) was calculated. Variables were converted into Z-scores from regression equations based on normal data. Features of fetuses with and without hydrops were compared. RESULTS: Higher effusion ratios were noted in hydropic versus non-hydropic fetuses. Compared to a normal population, study subjects had smaller dimensions of LV, RV and aortic and pulmonary valves. They also had higher pulmonary artery peak velocities. The comparison between non-hydropic and hydropic fetuses revealed lower values for LV and pulmonary valve dimensions, and peak aortic velocity in hydropic fetuses. The severity of LV compression correlated significantly with effusion ratio. CONCLUSION: Fetal hydrothorax is accompanied by compression of the cardiac structures, resulting in altered cardiac hemodynamics. Echocardiographic assessment, including the measurement of effusion ratio, may be a useful tool in guiding fetal therapy.

Blood Flow Velocity↗

Involvement of vacuolar H+ -ATPase in incorporation of risedronate into osteoclasts.

Although osteoclasts incorporate bisphosphonates during bone resorption, the mechanism of this incorporation by osteoclasts is not known. We previously reported that bisphosphonates disrupt the actin rings (clear zones) formed in normal osteoclasts, but did not disrupt actin rings in osteoclasts derived from osteosclerotic oc/oc mice, which have a defect in the gene encoding vacuolar H(+)-ATPase (V-ATPase). The present study showed that V-ATPase is directly involved in the incorporation of risedronate, a nitrogen containing bisphosphonate, into osteoclasts. Treatment of osteoclasts with risedronate disrupted actin rings and inhibited pit formation by osteoclasts on dentine slices. Bafilomycin A(1), a V-ATPase inhibitor, inhibited the pit-forming activity of osteoclasts but did not disrupt actin rings. Risedronate failed to disrupt actin rings in the presence of bafilomycin A(1). E-64, a lysosomal cysteine proteinase inhibitor, showed no inhibitory effect on the demineralization of dentine by osteoclasts but inhibited the digestion of dentine matrix proteins without disrupting actin rings. Risedronate disrupted actin rings even in the presence of E-64. Treatment of osteoclasts placed on plastic plates with risedronate also disrupted actin rings. Bafilomycin A(1) but not E64 prevented the disruption of actin rings in osteoclasts treated with risedronate on plastic plates. Inhibition of V-ATPase with bafilomycin A(1) also prevented disruption of actin rings by etidronate, a non-nitrogen-containing bisphosphonate. These results suggest that V-ATPase induced acidification beneath the ruffled borders of osteoclasts and subsequent bone demineralization triggers the incorporation of both nitrogen-containing and non-nitrogen-containing bisphosphonates into osteoclasts.

Actins↗

Destruxins, cyclodepsipeptides, block the formation of actin rings and prominent clear zones and ruffled borders in osteoclasts.

Bone-resorbing osteoclasts exhibit polarized morphological structures such as actin rings, clear zones, and ruffled borders. To gain insight into the mechanism of bone-resorbing activity of osteoclast and to discover new types of anti-resorptive agents, we have screened for natural compounds that inhibit the bone-resorbing activity of osteoclast-like multinucleated cells (OCLs). Destruxin B (DestB) and E (DestE), cyclodepsipeptides, were found to inhibit pit formation without affecting osteoclast differentiation and survival. Destruxins reversibly induced morphological changes in OCLs in a dose-dependent manner (DestB, 0.2-1 microM; DestE, 0.01-0.05 microM) and inhibited pit formation. Destruxin-induced morphological changes were accompanied by disruption of the actin rings in OCLs. The formation of actin rings in OCLs after adhesion was also inhibited by destruxins. Electron microscopical analysis revealed that destruxin-treated OCLs on dentine slices have no prominent clear zones and ruffled borders. The effective concentrations of destruxins on the morphological changes were almost the same as those that inhibited bone resorption in organ culture system. These results suggest that the anti-resorptive effects of destruxins result from induction of a disorder of the morphological structures in polarized OCLs.

Acid Phosphatase↗

Small vessel vasculitis limited to pleuropulmonary manifestations, possibly induced by endotoxin.

AIMS: We investigated a rare case of small vessel vasculitis (SVV) limited to pleuropulmonary manifestations, possibly induced by endotoxin, to determine the activation of immuno-mediated cells and endothelia in the pleuropulmonary circulation. METHODS AND RESULTS: A 44-year-old man with a high fever was X-rayed, revealing bilateral pleural effusion and atelectasis in the chest. His laboratory data were within normal limits except for a high white blood cell count and a high C-reactive protein level. Autoantibodies including anti-neutrophil cytoplasmic antibody were negative. Endotoxin was detected in his sera, but repeated cultures of sputa, urine, blood and the pleural effusion were negative for bacteria. Video-assisted thoracic surgery was performed and lung and parietal pleura specimens were obtained. Histology showed arterioles or small arteries infiltrated by monocytes or neutrophils with fibrinoid necrosis and acute or chronic venulitis. A diagnosis of SVV in the lung and pleura was made. Immunohistochemistry revealed that interleukin (IL)-1beta was expressed in monocytes and vascular cell adhesion molecule (VCAM)-1 on endothelial cells in the vasculitic lesions in the lung. CONCLUSIONS: Endotoxin possibly induced the inflammation in this apparently unique case of pleuropulmonary small vessel vasculitis. Immunohistochemistry revealed the expression of IL-1beta and VCAM-1 which may have caused activation of monocytes and endothelial cells within the vasculitic lesions.

Adult↗

Duodenal wall cysts may be derived from a ductal component of ectopic pancreatic tissue.

AIMS: To clarify the mechanism of origin of duodenal wall cysts in patients with chronic pancreatitis, developing into duodenal stenosis. METHODS AND RESULTS: Specimens from 12 pancreatoduodenectomized patients with chronic pancreatitis and 51 controls were studied histopathologically and immunohistochemically. Variously shaped cystic lesions, averaging about 15 mm in diameter, were found in the duodenum in six of the 12 patients with chronic pancreatitis, but were not observed in the controls. Each case had an average of two cysts, which were located mainly in the muscularis propria of the duodenum with or without submucosal or extraduodenal-peripancreatic extensions. The inner part of the cyst wall consisted of a moderate rim of granulation tissue, with both myofibroblasts and smooth muscle proliferation in the tissue surrounding the cyst and the submucosal layer of the duodenum, occasionally accompanied by an epithelial lining. A ductal structure in the muscularis propria of the duodenum, possibly a ductal component of ectopic pancreatic tissue, was found in five of the six cases. Some of these structures showed cystic changes. Three of the six patients had accompanying duodenal stenosis. CONCLUSIONS: Duodenal wall cysts occur mainly in the muscularis propria of the duodenum associated with both myofibroblasts and smooth muscle proliferation, and may result in duodenal stenosis. These cysts may be derived from a ductal component of ectopic pancreatic tissue.

Adult↗

ATP synthase: constrained stoichiometry of the transmembrane rotor.

Recent structural data suggest that the number of identical subunits (c or III) assembled into the cation-powered rotor of F1F0 ATP synthase depends on the biological origin. Atomic force microscopy allowed individual subunits of the cylindrical transmembrane rotors from spinach chloroplast and from Ilyobacter tartaricus ATP synthase to be directly visualized in their native-like environment. Occasionally, individual rotors exhibit structural gaps of the size of one or more subunits. Complete rotors and arch-shaped fragments of incomplete rotors revealed the same diameter within one ATP synthase species. These results suggest the rotor diameter and stoichiometry to be determined by the shape of the subunits and their nearest neighbor interactions.

ATP Synthetase Complexes↗

Monoclinic superstructure of SrMgF4 with perovskite-type slabs.

Crystals of Ce-doped SrMgF4, strontium magnesium tetrafluoride, have been found to have a monoclinic P2(1) structure with doubled a and tripled c cell lengths compared with the orthorhombic Cmcm structure previously reported in the literature. The perovskite-type slabs, composed of corner-sharing MgF6 octahedra and Sr atoms, are stacked along the b axis. The six crystallographically independent MgF6 octahedra are rotated so as to provide long periodicities along a and c. The coordination numbers and bond distances around the six crystallographically independent Sr atoms are slightly different in each case. In the superstructure, the Sr atoms lie on local mirror planes which are thought to originate at the high-temperature phase transition.

Journal Article↗

Quantitative trait locus analysis for chronic pancreatitis and diabetes mellitus in the WBN/Kob rat.

A causative gene mutation is still undefined in approximately half of patients with hereditary pancreatitis, and no genetic factor has been identified in most patients with sporadic chronic pancreatitis. To identify a pancreatitis-associated gene, we performed a quantitative trait locus (QTL) analysis for the traits of chronic pancreatitis and diabetes mellitus in WBN/Kob rats. We identified two highly significant QTLs for chronic pancreatitis and/or hyperinsulinemia on chromosomes 7 and X. These QTLs were located on completely different chromosomal regions from those of causative genes that have been reported for human chronic pancreatitis: PRSS1, CFTR, and SPINK1. For these QTLs, prevalences of the WBN/Kob allele significantly increased in the rats with chronic pancreatitis. These findings indicate that chronic pancreatitis in WBN/Kob rats is controlled by multiple genes, and a genetic analysis in WBN/Kob rats might be useful for gene targeting for human chronic pancreatitis.

Animals↗

Transcatheter coil closure of large patent ductus arteriosus with 0.052-inch Gianturco coils using myocardial biopsy forceps in a 70-year-old woman.

Small patent ductus arteriosus is generally closed in children using a transcatheter coil. This is done less often in older patients or those with large patent ductus arteriosus. We report successful antegrade transcatheter coil closure of patent ductus arteriosus in a 70-year-old woman. Into the patent ductus arteriosus, using flexible myocardial biopsy forceps, we placed two large 0.052-inch Gianturco coils, which were easily used as multipurpose vascular occlusion coils. The forceps and the coils were readily available and provided complete occlusion. Other delivery devices cannot deliver such large coils. Transcatheter coil closure thus appears to be safe and effective for closing large patent ductus arteriosus in the elderly.

Aged↗

Pancreatic ductal myofibroblasts. Proliferative patterns in various pathologic situations.

Myofibroblasts in the periacinar area of the pancreas have been demonstrated to mediate fibrogenesis in pancreatic fibrosis. However, only a few reports have described myofibroblasts in the pancreatic duct. To elucidate the presence of myofibroblasts in the pancreatic ductal wall, we performed an immunohistochemical study, using immunostains for both alpha-smooth muscle actin (alphaSMA) and desmin, and an electron microscopic study on surgically resected pancreatic specimens from 10, 23, 23, and 56 cases of focal pancreatitis (FP), chronic pancreatitis (CP), pancreatic carcinoma (PCa), and carcinoma of the papilla of Vater (VPCa), respectively. All cases showed localized stenosis of the main pancreatic duct by means of preoperative pancreatography. As controls, 20 autopsy cases were studied. alphaSMA-positive and desmin-negative cells existed in the ductal walls of controls and were revealed as myofibroblasts by means of electron microscopy. In six FPs, proliferation of myofibroblasts was observed at the stenotic portion. In VPCas, myofibroblasts mainly proliferated in the pancreatic ductal wall. In CPs and PCas, no myofibroblast proliferation was observed at the stenotic portion. The proliferation of myofibroblasts might occur as a wound healing process in FP, while acting against elevation of intraductal pressure in VPCa. In conclusion, proliferation of myofibroblasts plays an important role in ductal changes in various pathological situations.

Actins↗