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Biomedical subjects

Daisuke Suzuki

Publications and source records attributed to Daisuke Suzuki.

At least 37 records · Page 2Linked to original sources

Gold nanoparticle localization at the core surface by using thermosensitive core-shell particles as a template.

We report novel thermosensitive hybrid core-shell particles via in situ gold nanoparticle formation using thermosensitive core-shell particles as a template. This method for the in situ synthesis of gold nanoparticles with microgel interiors offers the advantage of eliminating or significantly reducing particle aggregation. In addition, by using thermosensitive microgel structures in which the shell has thermosensitive and gel properties in water--whereas the core itself is a water-insoluble polymer--we were able to synthesize the gold nanoparticles only at the surface of the core, which had reactive sites to bind metal ions. After the gold nanoparticles were synthesized, electroless gold plating was carried out to control the thickness of the gold nanoshells. The dispersions of the obtained hybrid particles were characterized by dynamic light scattering and UV-vis absorption spectroscopy, and the dried particles were also observed by electron microscopy. Adaptation of the technique shown here will create a number of applications as optical, electronic, and biomedical functional materials.

Gold↗

The positional effect of Ebeta on Vbeta genes of TCRbeta chain in the ordered rearrangement and allelic exclusion.

In the TCRbeta gene locus, the Vbeta, Dbeta and Jbeta gene segments are assembled in a tightly ordered manner. To investigate the positional effects of TCRbeta enhancer (Ebeta) on the recombination processes of the Vbeta genes, we utilized beta(LD) mice lacking 70% of the TCRbeta locus, leaving four Vbeta genes at the 5' side and, consequently, the Vbeta10 gene moves into the Ebeta regulatory region. In this mutant mouse, the Vbeta10 gene showed direct Vbeta-to-Dbeta and Vbeta-to-Jbeta recombination, although the Dbeta-to-Jbeta joining was still predominant. Interestingly, these two aberrant recombination processes were barely suppressed when beta(LD) mice were crossed with TCRbeta transgenic mice, whereas V(D)J recombination of the Vbeta10 gene was sufficiently suppressed. These results suggest that the positional effects of Ebeta on the Vbeta genes may enable the recombination potential to increase prior to Dbeta-to-Jbeta joining and that such aberrant recombination may be free from allelic suppression.

Animals↗

Modification of gold nanoparticle composite nanostructures using thermosensitive core-shell particles as a template.

We report the formation of novel thermosensitive hybrid core-shell particles via in situ synthesis of gold nanoparticles using thermosensitive core-shell particles as a template. The template core-shell particles, with cores composed mainly of poly(glycidyl methacrylate) (GMA) and shells composed mainly of poly(N-isopropylacrylamide) (PNIPAM), were synthesized in aqueous medium, and functional groups such as thiol groups were incorporated into each particle. We found that these particles containing thiol groups were effective for the in situ synthesis of gold nanoparticles in long-term storage. The obtained hybrid particles exhibited a reversible color change from red to purple, which originated from the surface plasmon resonance of gold nanoparticles and which was temperature-dependent in the range of 25-40 degrees C. In addition to their thermosensitive property, the hybrid particles exhibited the unique characteristic of uniform distribution on a solid substrate. The particles obtained by this approach have potential thermosensitive applications such as in sensors and photonic or electronic devices.

Journal Article↗

One-pot synthesis of metalated pyridines from two acetylenes, a nitrile, and a titanium(II) alkoxide.

Four-component coupling process involving two acetylenes, a nitrile, and a divalent titanium alkoxide reagent, Ti(O-i-Pr)(4)/2i-PrMgCl, directly yielded titanated pyridines in a highly selective manner. The reaction can be classified into four categories: (i) a combination of an internal acetylene, a terminal acetylene, sulfonylnitrile, and the titanium reagent to yield alpha-titanated pyridines, (ii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield alternative alpha-titanated pyridines, (iii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield titanated aminopyridines, and (iv) a combination of an acetylenic amide, a terminal acetylene, a nitrile, and the titanium reagent to yield pyridineamides with their side chain titanated. Some of these reactions enabled virtually completely regioselective coupling of two different, unsymmetrical acetylenes and a nitrile to form a single pyridine. Synthetic applications of these reactions have been illustrated in the preparation of optically active pyridines and medicinally useful compounds.

Journal Article↗

Facile preparation of various heteroaromatic compounds via azatitanacyclopentadiene intermediates.

Coupling of acetylene, nitrile, and a titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, generated new azatitanacyclopentadienes in a highly regioselective manner. Their subsequent reaction with sulfonylacetylene afforded pyridyltitanium compounds, which, upon reaction with electrophiles, gave substituted pyridines virtually as a single isomer. When optically active nitriles were used in this reaction, chiral pyridines were obtained without loss of the enantiopurity. Alternatively, the azatitanacyclopentadiene prepared from an unsymmetrical acetylene reacted with an aldehyde or another nitrile to give furans or pyrroles having four different substituents again in a regioselective manner.

Journal Article↗

Novel serpinopathy in rat kidney and pancreas induced by overexpression of megsin.

The intracellular polymerization of abnormal serine protease inhibitors (serpins) results in liver or neuronal cell abnormalities recently identified as "serpinopathies." It was demonstrated in transgenic rats that overexpression of megsin, a recently discovered serpin located in the kidney, produces renal and pancreatic lesions characteristic of serpinopathies. Megsin expression is elevated in a variety of organs, including kidney and pancreas. Periodic acid-Schiff-positive, diastase-resistant intracellular inclusions develop only in the kidney and the pancreas. They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy. In the kidney, inclusions are located mainly in the endoplasmic reticulum of glomerular epithelial, distal, and collecting duct cells, and are associated with massive proteinuria and an impaired renal function. In the pancreas, similar inclusions are found in the exocrine and Langerhans islet cells, where islet beta cells are reduced as a result of apoptosis. They are associated with diabetes with low insulin levels. The animals have an impaired growth and die within 10 wk. Rats that overexpress a mutant megsin, characterized by a deficient conformational transition activity, do not develop the serpinopathy, suggesting that some conformational flexibility of the serpin is required for the development of serpinopathy. This model of serpinopathy is the first to involve the kidney and the pancreas.

Animals↗

Heterogeneity of subvesical ducts or the ducts of Luschka: a study using drip-infusion cholangiography-computed tomography in patients and cadaver specimens.

The objective of this study was to examine the heterogeneity of the subvesical duct or the ducts of Luschka as well as the reliability of drip-infusion cholangiography with computed tomography (DIC-CT) for their identification. DIC-CT was used in 277 consecutive patients (135 men, 142 women) and for the dissection and histologic study of 10 cadaver livers. We found 32 subvesical ducts in 28 (10.1%) of 277 patients. Irrespective of whether the terminals were extra- or intraparenchymal, the subvesical ducts often (17/32 ducts, 15/28 patients) drained into a subsegmental duct of S5 or S4. Notably, some displayed an "intermediate" course along the gallbladder fossa with an intraparenchymal origin and terminated at S5. Such ducts tended to be seen in the elderly. Another 15 ducts drained into a thick, centrally located duct, such as the right sectorial or hepatic duct. The anatomic study demonstrated that the subvesical duct likely included the cystic vein-concomitant duct. A major type of subvesical duct, characterized by an intermediate course along its bed, appeared to result from degenerative exposure of a peripheral duct with aging. The subvesical duct draining into the thick duct included both a "daughter branch," such as seen in the lung, and the so-called anomaly. Such ducts can be demonstrated with DIC-CT, but the incidence might be limited. However, the cystic vein/concomitant duct was difficult to identify radiologically. Consequently, although presurgical radiology is useful for avoiding bile leakage after laparoscopic cholecystectomy, surgeons should be aware of its limitations.

Adolescent↗

Topographical histology of the posterolateral corner of the knee, with special reference to laminar configurations around the popliteus tendon: a study of elderly Japanese and late-stage fetuses.

We investigated the histology of laminar configurations at the posterolateral corners of 40 knees (18 late-stage fetuses, 22 elderly persons). In the fetuses, the deeply located popliteal fascia and the superficially located inferior geniculate vascular sheath were evident in a space between the popliteus tendon (PT) and the biceps femoris and gastrocnemius. Along, and deep to, the popliteal fascia, the popliteus muscle parenchyma developed into both the PT and another dense connective tissue mass. The PT attached to the fibula (i.e., the fetal popliteofibular ligament) and to the base of the lateral meniscus (i.e., the fetal popliteomeniscal fasciculus). This laminar configuration was essentially maintained in the elderly. The fetal dense connective tissue of the popliteus origin seemed to correspond to the adult arcuate ligament. However, because a connective tissue complex (including the PT and the arcuate and popliteofibular ligaments) was often well developed, the complex involved the inferior geniculate vascular sheath and popliteal fascia. A spectrum of variations was found in how thickly the complex developed. Thus, clear separation of the PT from the surrounding tissues often became difficult. Notably, the connective tissue complex could be peeled in different manners, depending on the site and the individual. Therefore, macroscopic variation in the posterolateral corner, including the apparent absence of some ligaments, seemed to be related to the thickness and number of layers developed by the connective tissue complex, possibly due to an adaptation to the individual's mechanical environment during growth and aging.

Aged↗

Time-resolved electron paramagnetic resonance of the lowest excited triplet state of phenazinium cation.

Time-resolved and steady-state electron paramagnetic resonance (EPR) spectra have been observed for the lowest excited triplet (T(1)) states of phenazine (Phz) and its singly protonated cation (phenazinium) in sulfuric acid-ethanol mixtures at 77K. The single protonation appears to have little effect on the anisotropic sublevel populating rates of the T(1) state of phenazine. However, the zero-field splitting (ZFS) parameter D decreases on the protonation, reflecting the increase of delocalization of the two unpaired electrons. The sublevel preferentially populated by intersystem crossing (ISC) is T(y) in both phenazine and phenazinium (the y-axis is parallel to the in-plane long axis). From the analysis of the observed anisotropy in the ISC rates and the semi empirical molecular orbital calculations of the ZFS parameters, we concluded that the T(1) state of phenazinium is the (3)A(1)(pipi*) state.

Cations↗

Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy.

BACKGROUND: In diabetic nephropathy (DN) small vessels are frequently observed around the glomerular vascular pole in addition to normal afferent and efferent arterioles; this is regarded as neovascularization . Because vascular endothelial growth factor (VEGF) promotes vascular generation, the authors investigated the relationship between glomerular VEGF gene expression and structural glomerular changes in the early stage of human DN. METHODS: Kidney specimens were obtained from 18 type 2 DN patients by open renal biopsy. Additional vessels were distinguished by light microscopy as either afferent or efferent arterioles. Glomerular VEGF messenger RNA expression was determined by using in situ hybridization. The mesangial matrix area was quantified, and the ratio of the mesangial matrix area to the whole glomerular area was calculated to determine the mesangial matrix index (MMI). RESULTS: There were significantly more glomeruli with extra vessels in DN than in normal kidneys. The degree of neovascularization was significantly increased in DN and correlated with the magnitude of VEGF messenger RNA expression (r 2 = 0.46, P = 0.010) and MMI (r 2 = 0.45, P = 0.0093). CONCLUSION: These findings suggest that glomerular VEGF may be involved in structural changes in human DN at an early stage.

Adult↗

Structure and component alteration of rabbit Achilles tendon in tissue culture.

The aim of this study was to investigate alterations of cultured tendon tissues to determine whether tissue culture is a useful method for biological analyses of the tendon. Tendon tissues for tissue culture were isolated from Achilles tendons of rabbits. The tendon segments were placed one segment per well and incubated in growth medium consisting of Dullbecco's modified Eagle's medium supplemented with 5% fetal bovine serum at 37 degrees C in a humidified atmosphere with 5% CO(2) for various periods. The alignment of collagen fibrils was preserved for 48 h, but tendon structure has disintegrated at 96 h. Alcian blue staining and gelatine zymography revealed that proteoglycan markedly diminished and that matrix metalloproteinase (MMPs) activity was upregulated sharply at 72 and 96 h. The ratio of collagen fibrils with large diameter had increased and the mean diameter and mass average diameter value had reached maximum at 48 h. The values then decreased and mean diameters at 72 and 96 h were significantly different from that at 48 h. At 96 h, the ratio of collagen fibrils with small diameters had increased and collagen fibrils with large diameters had disappeared. These findings indicate that structural alteration is possible to be induced by disintegration of collagen fibrils and disappearance of glycosaminoglycans from extracellular matrix (ECM), subsequent of upregulation of MMPs activity. Although the study period is limited, the tissue culture method is available for investigating cell-ECM interaction in tendons.

Achilles Tendon↗

Re-entrant volume phase transition of hydrogel membrane of microcapsule.

Re-entrant volume phase transition of hydrogel wall membrane of microcapsules (MC) was first observed using MC suspensions consisting of poly (L-lysine-alt-terephthalic acid) wall and aqueous inner and outer solutions with different pHs. To analyze the dynamics of the re-entrant phase transition, we extended the theory for the swelling and the shrinking dynamics of the microcapsule gel [T. Narita, T. Yamamoto, D. Suzuki, T. Dobashi, Langmuir 19 (2004) 4051]. In the theory, the microcapsule size and the force constant for the driving force which gives rise to the size relaxation were chosen as the thermodynamic variables. The time course of the cross-sectional area of the microcapsules fitted well to the theoretical equations, and the time constants determined as the fitting parameters were discussed in terms of the force constant relaxation and the size relaxation.

Hydrogels↗

Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo.

Notch receptors and their ligands contribute to many developmental systems, but it is not apparent how they function after birth, as their null mutants develop severe defects during embryogenesis. Here we used the Cre-loxP system to delete the Delta-like 1 gene (Dll1) after birth and demonstrated the complete disappearance of splenic marginal zone B cells in Dll1-null mice. In contrast, T cell development was unaffected. These results demonstrated that Dll1 was dispensable as a ligand for Notch1 at the branch point of T cell-B cell development but was essential for the generation of marginal zone B cells. Thus, Notch signaling is essential for lymphocyte development in vivo, but there is a redundancy of Notch-Notch ligand signaling that can drive T cell development within the thymus.

Adaptor Proteins, Signal Transducing↗

Does the fabella contribute to the reinforcement of the posterolateral corner of the knee by inducing the development of associated ligaments?

The fabellofibular (FF) and arcuate ligaments are closely colocated at the posterolateral corner of the knee. However, a bony fabella is often absent in Japanese subjects. We investigated these structures morphometrically using 212 knees. A thick FF ligament was found in 38.1% (40/105) of knees with a hard fabella. When identified histologically, a bony fabella accompanied a thick FF in 82.8% (24/29). Conversely, a thin or indefinite FF ligament and an elastic-textured fabella co-existed in 77.9% (60/70) of knees. There were no strong correlations between the morphology of the fabella and the arcuate ligament. Thus, a hard or bony fabella seemed to relate to thickening of the FF ligament. In contrast, the thicknesses of the FF and arcuate ligaments were negatively correlated. When the FF ligament was more than 5 mm thick, indicating that it was as strong as the lateral collateral ligament, no arcuate ligament could be identified. Conversely, a thin or indefinite FF ligament often accompanied a well-developed arcuate ligament (61.9%, 96/155). Our observations suggest that these ligaments act in a complementary manner to stabilize the posterolateral corner. A possible common function is fixation of the popliteal tendon on the joint capsule and lateral meniscus, rather than direct stabilization against rotation stress.

Aged↗

Glomerular expression of platelet-derived growth factor (PDGF)-A, -B chain and PDGF receptor-alpha, -beta in human diabetic nephropathy.

BACKGROUND: Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN. METHODS: We examined open renal biopsies of 20 type 2 diabetic patients with DN, and 10 normal human kidneys (NHK). Histopathologically, the severity of DN was classified as grade I (DN I, n = 10; mild mesangial expansion) or grade II (DN II, n = 10; moderate mesangial expansion). We evaluated the expression and localization of PDGF-A, -B, and PDGFR-Alpha, -Beta using in situ hybridization, and quantified PDGF and PDGFR mRNA expression by counting all nuclei, and nuclei surrounded by PDGF-positive cytoplasm and PDGFR-positive cytoplasm, in at least ten randomly selected cross-sections of nonsclerotic glomeruli. RESULTS: In all glomeruli, PDGF and PDGFR mRNAs were expressed mainly in glomerular resident cells, predominantly glomerular mesangial and epithelial cells. The percentages of cells positive for PDGF-A and PDGFR-Alpha mRNA in DN were similar to those in NHK. In contrast, the percentages of PDGF-B and PDGFR-Beta mRNA-positive cells in DN were significantly higher than those in NHK, and were significantly higher in DN I than in DN II: The percentages of cells positive for PDGF-B correlated with the PDGFR-Beta mRNA level. CONCLUSIONS: Our results suggest that the expression of PDGF-B and PDGFR-Beta is an important factor in histologically early glomerular lesions of DN. Mesangial expansion is thought to be a major cause of diabetic nephropathy (DN). Platelet-derived growth factor (PDGF) plays an important role in the production of extracellular matrix proteins in renal diseases. The present study was designed to determine the expression of PDGF and PDGF receptor (PDGFR) mRNA in the renal tissues of type 2 diabetic patients with DN.

Adult↗

Neutral-pH peritoneal dialysis solution improves peritoneal function and decreases matrix metalloproteinase-2 (MMP-2) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

BACKGROUND: Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs), and these characteristics contribute to membrane dysfunction in PD patients. The formation of GDPs can be reduced by separating the glucose component of the solution from the lactate component during sterilization. This study was carried out to evaluate the clinical effect of dual-chambered neutral-pH PD solution in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Thirteen CAPD patients using conventional PD solution were enrolled in this study. The fast peritoneal equilibration test (fast PET) was performed periodically before and after treatment with neutral PD solution. The concentration of matrix metalloproteinase-2 (MMP-2) in dialysate effluent was measured using 4-h dwelling 2.5% glucose dialysis solution. The patients were categorized into two groups, according to the value of the initial dialysate/plasma (D/P) creatinine ratio: i.e., lower transporters (group L, D/PCr < 0.65) and higher transporters (group H, D/PCr >/= 0.65). RESULTS: The mean D/P creatinine ratio measured by fast PET, was significantly decreased (0.72 +/- 0.09 to 0.60 +/- 0.06; P < 0.03) after treatment with neutral PD solution in group H. The mean glucose level in 4-h dwelling dialysate effluent was elevated (824.6 +/- 195.9 mg/dl to 942.6 +/- 147.8 mg/dl; P < 0.022) in all subjects. In group H, a significant decrease of MMP-2 in the dialysate effluent was recognized from 15 months after the beginning of treatment with the neutral PD solution (141.4 +/- 52.5 ng/ml to 91.3 +/- 15.1 ng/ml; P < 0.05), with the lowest value being shown at 21 months (80.0 +/- 31.8 ng/ml; P < 0.03). CONCLUSIONS: Neutral-pH peritoneal dialysis solution decreased the MMP-2 level in dialysate and improved peritoneal function in high-transporter patients with CAPD treatment.

Adult↗