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Biomedical subjects

Y Takakura

Publications and source records attributed to Y Takakura.

At least 37 records · Page 2Linked to original sources

Subtalar arthrography in recurrent instability of the ankle.

Subtalar arthrography was done in 37 feet of 35 patients in whom recurrent instability of the ankle was diagnosed. There were 16 male and 19 female patients, with a mean age of 29.1 years (range, 11-56 years). The mean interval between the injury and arthrography was 4 years 3 months (range, 6 months-22 years). Anteroposterior, lateral, and oblique radiographs were obtained for all patients. Any leakage during arthrography into the ankle, tendon sheaths, or sinus tarsi was recorded. An oblique view of the microrecess along the interosseous ligament and an anteroposterior view of the lateral recess just under the end of the fibula were examined. At surgery, 13 feet had combined injuries of the anterior talofibular and calcaneofibular ligaments, and 24 feet had isolated injury of the anterior talofibular ligament. The findings of the two groups were significantly different when examined for leakage into the ankle, leakage into the peroneal tendon sheath, and the presence of the lateral recess. Presence of contrast medium in at least two of these three positive arthrographic findings showed 92.3% sensitivity and 87.5% specificity in making the diagnosis of calcaneofibular ligament injury. Subtalar arthrography is valuable in making the diagnosis of calcaneofibular ligament injury in recurrent instability of the ankle.

Adolescent↗

Static scapholunate dissociation diagnosed by scapholunate gap view in wrists with or without distal radius fractures.

This prospective study investigated static scapholunate dissociation (SLD) in wrists associated with distal radius fractures. SLD was detected as a widening of the scapholunate (SL) joint interval by SL gap view. Ninety-six distal radius fractures and 154 normal wrists were investigated by SL gap view, which is better for detecting SLD than the standard posteroanterior (PA) view. Incidences of non-symptomatic SLD detected by SL gap view in normal wrists increased by age. In the young age bracket, incidences of SLD in distal radius fractures were significantly higher than in normal wrists. Our results indicated that in patients younger than 30 years old, SLD in distal radius fractures was a fracture-caused abnormality. In those over 30, ascribing SLD to the fracture was difficult. Close examinations, like arthroscopy and dynamic cineradiography, need to be made in patients with SLD associated with distal radius fractures, especially in those younger than 30.

Adolescent↗

Fixation of osteochondral lesions of the talus using cortical bone pegs.

We have treated osteochondral lesions of the talus using cortical bone pegs. We examined 27 ankles (27 patients) after a mean follow-up of 7.0 years (2 to 18.8). The mean age of the patients was 27.8 years (12 to 62). An unstable osteochondral fragment or osteosclerotic changes in the bed of the talus were regarded as indications for the procedure. The clinical results were good in 24 ankles (89%) and fair in three (11%); none had a poor result. There was also radiological improvement in 24 ankles. Repair of the articular surface and stability of the lesion can be achieved even in unstable chronic lesions.

Adolescent↗

Surface hydrophobicity of particles is not necessarily the most important determinant in their in vivo disposition after intravenous administration in rats.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) and lecithin-coated MS-50 (LMS-50) after intravenous administration to rats was characterized. While a rapid elimination from the systemic circulation was observed for MS-50, much more prolonged circulating property was observed for LMS-50. In addition, this in vivo disposition property of LMS-50 was suggested to be ascribed to its lower affinity to the liver, which is the determining organ of the in vivo disposition of MS-50. The evaluation of surface hydrophobicity of MS-50 and LMS-50 in buffer solution revealed that the surface of MS-50 is more hydrophobic than that of LMS-50. However, LMS-50 was oppositely found to be more hydrophobic than that of MS-50 in rat serum. The profiles of serum proteins associated with MS-50 and LMS-50 were also examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results showed that the amounts of some adsorbed proteins are greatly different between MS-50 and LMS-50. From these findings, it was suggested that the substantial difference in the in vivo disposition between MS-50 and LMS-50 would not be attributed to the difference in their surface hydrophobicity in the blood, but the difference in the type of serum proteins associated with them.

Animals↗

Synthesis and pharmacological activity of a novel water-soluble hepatocyte-specific polymeric prodrug of prostaglandin E(1) using lactosylated poly(L-glutamic hydrazide) as a carrier.

A novel polymeric prodrug of prostaglandin E(1) (PGE(1)) was synthesized using lactosylated poly(L-glutamic hydrazide) (Lac-NH-PLGA) as a targetable carrier to hepatocytes. Poly(L-glutamic hydrazide) (PLGA-HZ) was prepared by reacting poly(gamma-benzyl-L-glutamate) with hydrazine monohydrate, followed by coupling with lactose via a hydrazone linkage. Then the lactosylated PLGA-HZ was reduced by sodium cyanoborohydride (NaBH(3)CN) in order to make the linkage irreversible (Lac-NH-PLGA). Finally, PGE(1) was bound to hydrazide moieties remaining in Lac-NH-PLGA without any condensing agent under weakly acidic conditions (pH 5) where PGE(1) would be chemically most stable at room temperature (PGE(1) conjugate). The PGE(1) conjugate prepared was sufficiently water-soluble in spite of the hydrophobic nature of its backbone (-NH-CH-CO-) and PGE(1) itself. After intravenous injection in mice, the [111In]PGE(1) conjugate rapidly accumulated in the liver, whereas [111In]PLGA-HZ did not, suggesting the involvement of a galactose-specific mechanism in the uptake of the [111In]PGE(1) conjugate. Fractionation of liver cells revealed that the [111In]PGE(1) conjugate was preferentially taken up by liver parenchymal cells. The pharmacological activity was examined in mice with fulminant hepatitis induced by intraperitoneal injection of carbon tetrachloride. Intravenous injection of the PGE(1) conjugate at a dose of 1 mg (0.065 mg PGE(1))/kg effectively inhibited the increase in plasma glutamic pyruvic transaminase (GPT) activity compared with that of free PGE(1) at a dose of 0.065 or 0.65 mg/kg. These results suggest that the PGE(1) conjugate is an excellent prodrug for the treatment of fulminant hepatitis.

Acute Disease↗

Cell-specific delivery of genes with glycosylated carriers.

Cationic liposomes and polymers have been accepted as effective non-viral vectors for gene delivery with low immunogenicity unlike viral vectors. However, the lack of organ or cell specificity sometimes hampers their application and the development of a cell-specific targeting technology for them attracts great interest in gene therapy. In this review, the potential of cell-specific delivery of genes with glycosylated liposomes or polymers is discussed. Galactosylated liposomes and poly(amino acids) are selectively taken up by the asialoglycoprotein receptor-positive liver parenchymal cells in vitro and in vivo after intravenous injection. DNA-galactosylated cationic liposome complexes show higher DNA uptake and gene expression in the liver parenchymal cells in vitro than DNA complexes with bare cationic liposomes. In the in vitro gene transfer experiment, galactosylated liposome complexes are more efficient than DNA-galactosylated poly(amino acids) complexes but they have some difficulties in their biodistribution control. On the other hand, introduction of mannose residues to carriers resulted in specific delivery of genes to non-parenchymal liver cells. These results suggest advantages of these glycosylated carriers in cell-specific targeted delivery of genes.

Amino Acid Sequence↗

Optical resonance in a narrow slit in a thick metallic screen.

Interaction of TM-polarized waves with a subwavelength thick metallic slit has been analyzed. A Fabry-Pérot-like behavior is reported. The resonance peaks, however, have very low magnitude and a systematic shift towards longer wavelengths is observed. The slit being narrow, this shift can be interpreted as the result of an aperture effect. Spectral transmission from a periodic array of such slits features the same peaks with a high increase in their magnitude, confirming that a grating acts as an amplifier of those resonances. Such a mechanism might explain the enhancement of the transmission observed in recent experiments [T. W. Ebbesen, H. J. Lezec, H. F. Ghaemi, T. Thio, and P. A. Wolff, Nature (London) 391, 667 (1998)].

Journal Article↗

Biliary excretion of polystyrene microspheres depends on the type of receptor-mediated uptake in rat liver.

Hepatic uptake and biliary excretion of fluorescein isothiocyanate-labeled polystyrene microspheres with a particle size of 50 nm (MS-50) were studied in rats. Liver perfusion studies revealed that not only apo-E-mediated but also asialoglycoprotein receptor-mediated uptake is involved in the mechanism of the serum protein-dependent uptake of MS-50 in the liver. The uptake of MS-50 mediated by apo-E contributes more to the total uptake of MS-50 by the hepatocytes than that via asialoglycoprotein receptor in the presence of serum in the perfusate. Furthermore, it was found that MS-50 is substantially excreted into the bile by transcytosis. The extent of exocytosis of MS-50 taken up by the hepatocytes was much higher after MS-50 was endocytosed via asialoglycoprotein receptor than after taken up via the process mediated by apo-E. On the basis of these results, a possible regulation of the intracellular sorting of ligands, depending on the receptor-mediated uptake mechanism, was inferred.

Animals↗

The fate of poly(2-dimethyl amino ethyl)methacrylate-based polyplexes after intravenous administration.

Poly(2-dimethyl amino ethyl) methacrylate (pDMAEMA) cationic polymers have been shown to be efficient vectors for gene delivery in vitro. This contribution deals with the in vivo properties of polyplexes based on this polymer. In mice, pDMAEMA/[32P]-pLuc complexes distributed primarily to the lungs. The gene expression profile matched the biodistribution profile. In vitro turbidity experiments in serum showed severe aggregation upon addition of cationic polyplexes, pointing out the involvement of aggregates in the dominant lung uptake of the positively charged polyplexes. Incubations of polyplexes with albumin yielded a decline of the zeta potential of the complexes to negative values, making an electrostatic mechanism in the dominant lung uptake less likely. Hemagglutination experiments showed that the polyplexes induce the formation of extremely large structures when incubated with washed erythrocytes. Altogether, the present data indicate that aggregate formation and trapping of the formed aggregates in the lung capillary bed is probably responsible for the dominant lung uptake and transfection. Poly(ethylene)glycol (PEG) of the polymeric structures prevented the increase in the observed turbidity in serum seen with polyplexes and was also able to reduce interactions with erythrocytes. Currently, the in vivo fate of the PEGylated polyplexes is under investigation.

Animals↗

Evaluation of the longitudinal arch of the foot with hallux valgus using a newly developed two-dimensional coordinate system.

The purposes of the present study were to establish a method for the evaluation of the longitudinal arch, using a two-dimensional coordinate system, and to clarify the main point of flattening of the foot in patients with hallux valgus. Measurements on a weight-bearing lateral radiograph of the foot were performed in 186 feet of 110 women with symptomatic hallux valgus and in 93 normal feet of 72 women. A two-dimensional coordinate system was used to perform the measurements. In this coordinate system, the line connecting the lowest point of the first metatarsal head and the lowest point (O) of the calcaneus is fixed as the x-axis, and the line that is perpendicular to the x-axis and intersects the x-axis at point O is fixed as the y-axis. The mean values of the y-coordinates at the points of the medial longitudinal arch of the foot in the patients with hallux valgus were significantly lower than those in the normal subjects (P < 0.001). The values were noticeably lower at points on the navicular. However, no change was observed in the posterior talus body. The new coordinate system indicated that the main points of flattening of the foot in patients with hallux valgus were the plantar flexion of the talus and the sinking of the navicular.

Adolescent↗

Neurohistochemical analysis of regeneration in rat peripheral nerve after end-to-side neurorrhaphy.

We investigated the regenerative capacity of motor nerves repaired by end-to-side or end-to-end neurorrhaphy, using choline-acetyltransferase (ChAT) activity measurement or histological analysis. The right medial gastrocnemius nerves (MGNs) of 62 male Fisher strain rats were transected and divided into three groups. In group 1, the distal ends of the MGN were coapted to the side of the lateral gastrocnemius nerve, using a Y-shaped silicone tube in end-to-side neurorrhaphy. In group 2, the nerve ends were reconnected by the traditional end-to-end technique. In group 3, the nerve ends were separated and remained unrepaired. The MGNs were sampled 1, 2, and 3 months postoperatively for histological examinations and ChAT activity measurement. The medial gastrocnemius muscle (MGM) was also sampled for histological evaluations. Axonal regeneration of MGN and the recovery of MGM to nearly normal histology and weight were observed in groups 1 and 2 3 months postoperatively. Although there were no significant differences in ChAT values between groups 1 and 2, the values were significantly larger than that of group 3 3 months postoperatively. These findings suggested that end-to-side neurorrhaphy would be an alternative treatment for peripheral nerve injury in certain clinical situations.

Animals↗

Development of gene drug delivery systems based on pharmacokinetic studies.

A series of pharmacokinetic studies following systemic or local administration for the development of delivery systems for gene drugs, such as plasmid DNA and oligonucleotides, are reviewed. The pharmacokinetics of gene drugs after intravenous injection into mice was evaluated based on clearance concepts. Pharmacokinetic analysis revealed that the overall disposition characteristics of the gene drug itself were determined by the physicochemical properties of its polyanionic DNA. Based on these findings, liver cell-specific carrier systems via receptor-mediated endocytosis were successfully developed by optimizing physicochemical characteristics. On the other hand, the pharmacokinetics of gene drugs after intratumoral injection were assessed in a tissue-isolated tumor perfusion system. The relationship between the physicochemical properties of gene drug delivery systems and intratumoral pharmacokinetics was determined and the therapeutic effect was also discussed in relation to pharmacokinetics. Collectively, it was demonstrated that a rational design of gene drug delivery systems that can control their in vivo disposition is possible by means of pharmacokinetic studies at whole body, organ and cellular levels.

Animals↗

Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol or DOPE as a helper lipid in the single-pass rat lung perfusion system.

Plasmid DNA-cationic liposome complexes (lipoplexes) accumulate in the lung to a great extent immediately after intravenous administration, and gene expression occurs predominantly in the lung. However, the detailed mechanisms underlying the lung accumulation of lipoplexes are not fully understood. In this study, we investigated the effect of blood components on the lung accumulation of lipoplexes using a single-pass rat lung perfusion system. Two types of lipoplexes, Chol-containing lipoplex ([(32)P]DNA-DOTMA/Chol liposome complex) and DOPE-containing lipoplex ([(32)P]DNA-DOTMA/DOPE liposome complex), pre-incubated with whole blood, serum, or erythrocytes, were injected into the perfused lung via an artery. Similarly to in vivo observations, extensive lung accumulation was observed for both types of lipoplexes after incubation with whole blood during a single passage. The (32)P-labeled lipoplexes pre-incubated with erythrocytes showed similar lung accumulation, whereas their lung accumulation after incubation with serum was significantly reduced, suggesting that erythrocytes would be more responsible blood components for extensive uptake by the perfused lung. However, there was a clear difference in the amounts of the accumulated erythrocytes after intra-arterial injection between the two lipoplex formulations. A significant degree of erythrocyte accumulation was observed when the DOPE-containing lipoplex was injected, whereas the Chol-containing lipoplex failed to induce any significant erythrocyte accumulation in the lung. In vitro experiments showed that the major fraction of both lipoplexes was bound to erythrocytes. These data suggested that Chol-containing lipoplexes bound to erythrocytes before injection dissociate from the erythrocytes and are transferred to the lung capillary endothelial cells during their passage through the lung. In contrast, DOPE-containing lipoplexes bound to erythrocytes cause aggregation and are embolized in the lung capillary with erythrocytes. Thus, the present study demonstrated that the interaction with erythrocytes plays an important role in the lung accumulation of lipoplexes and that neutral helper lipid significantly affects this interaction.

Animals↗

Interaction between DNA-cationic liposome complexes and erythrocytes is an important factor in systemic gene transfer via the intravenous route in mice: the role of the neutral helper lipid.

Recent studies have indicated that there are many barriers to successful systemic gene delivery via cationic lipid vectors using the intravenous route. The purpose of this study was to investigate the effect of binding and interaction between erythrocytes, a major constituent of blood cells, and the complexes, in relation to the role of the helper lipid, on the in vivo gene delivery to the lung following intravenous injection. We used three types of cationic lipid vectors, DNA-DOTMA/Chol liposome complexes, DNA-DOTMA liposome complexes, and DNA-DOTMA/DOPE liposome complexes. Although the three types of vectors bind to murine blood cells in vivo and in vitro, DOTMA/Chol and DOTMA complexes with a higher in vivo transfection activity do not induce fusion between erythrocytes, whereas DOTMA/DOPE complexes, a less efficient vector in vivo, induce fusion between the erythrocytes after a short incubation period. Pre-incubation of DOTMA/DOPE complexes with erythrocytes significantly reduced the transfection efficiency while DOTMA/Chol- and DOTMA complexes were more resistant to such treatment. The differences in the physicochemical and structural properties of these complexes could explain the differences in interaction with erythrocytes and subsequent gene expression. Lipids in DOTMA/Chol and DOTMA complexes have a stable lamellar structure. However, lipids in DOTMA/DOPE complexes have a highly curved structure with high fluidity. These results indicate that the interaction with erythrocytes depends on the properties of the cationic lipid vectors and this is an important factor for intravenous gene delivery using cationic lipid vectors.

Animals↗

Primary osteogenic sarcoma of a finger proximal phalanx: a case report and literature review.

Osteogenic sarcoma of the small bones of the hand is rare with only 15 cases documented. We describe a 12-year-old boy with an osteogenic sarcoma of the proximal phalanx of the middle finger. Wide excision in the form of ray amputation with a wide surgical margin was performed after neoadjuvant chemotherapy consisting of combined high-dose methotrexate, doxorubicin, ifosfamide, and cisplatin. To restore maximum function the index ray was transferred to the base of the third metacarpal. Adjuvant chemotherapy was administered subsequently. At 28-month follow-up evaluation there was no evidence of local recurrence of disease or distant metastasis and both function and appearance were good.

Amputation, Surgical↗

Distal cement mantle thickness with a triangular distal centralizer inserted into the stem tip in cemented total hip arthroplasty.

Fifty-seven hips undergoing a primary cemented total hip arthroplasty with use of a triangular distal centralizer inserted into the stem tip were investigated, with a special focus on distal cement mantle thickness. The subjects were 43 women and 3 men. When evaluated on conventional anteroposterior and lateral radiographs, the relative incidence of thin cement mantles in zones 3 or 5 owing to the distal centralizer was 15.8% (9 hips). Unsatisfactory findings were that the distal centralizer and distal part of the stem shifted to the cortex in 7 hips and bent or failed at the inserted site in 2 hips. There is risk of generating a thin cement mantle with use of the triangular centralizer and its insertion into the stem tip.

Adult↗

Clinical application of the reversed pedicled venous flap containing perivenous areolar tissue and/or nerve in the hand.

A reversed pedicled venous flap containing perivenous areolar tissue and/or nerve was used to cover traumatic skin defects of seven fingers in six patients. The series consisted of six men, ranging in age from 20 to 57 years (average: 39 years). The reconstructed sites were four dorsal skin defects and three volar skin defects of the finger. The flap was designed on the dorsum of the hand, in such a way as to place a vein at the centre of the flap and not to involve the dorsal metacarpal artery. The flap contained a dorsal vein, perivenous areolar tissue and fascia of the interosseous muscle. Cutaneous nerves were present in three of the seven flaps. The pedicle of the flap was dissected distally to the finger web space and the flap was transferred to the skin defect. The size of the flap ranged from 1.4x4.5 cm to 6.0x7.0 cm. The average length of the pedicle was 1.6 cm. Skin grafting was needed at the donor site in one case (flap size: 6.0x7.0 cm), but primary closure was possible in the remaining cases. Postoperatively, the largest flap showed superficial necrosis, although it survived. The remaining flaps survived completely. This suggests that in a large flap the skin should be attached to the pedicle to prevent congestion. The flap can be elevated without reference to the dorsal metacarpal artery at the ulnar side of the dorsum of the hand. The flap is an effective option to reconstruct skin defects of the finger, especially the little finger.

Adult↗

Viability of ischemia/reperfused bone determined at the gene expression level.

Rat bone viability was evaluated, using a bone viability index (BVI) that reflects mRNA degradation. To evaluate ischemic injury of the bone, 28 amputated hind limbs of Fischer rats (ischemic insult group: four subgroups, each containing seven limbs) were preserved at normothermia for 1, 3, 6 and 9 hr and the tibiae were harvested. To investigate ischemia/reperfusion injury, another 42 amputated limbs were transplanted to recipient Fischer rats after ischemia at normothermia for 1, 3 and 6 hr, respectively. The tibiae from the transplanted limbs were harvested on day 3 and day 7 after the transplantation (ischemia/reperfusion group). Seven fresh tibiae were also harvested and used as controls (control group). The total RNA isolated from the tibia of each group was fractionated by electrophoresis and hybridized with 32P-labelled cDNA of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the radioactivity of intact and degraded GAPDH mRNA was measured. BVI was calculated as follows: BVI = [A/(A + B)] x 100, where A and B represent the radioactivities corresponding to the intact GAPDH and degraded GAPDH mRNA band, respectively. In the 1-hr and 3-hr ischemia groups, the BVIs of the ischemia/reperfused group were comparable to those of controls, although the indexes of the ischemic insult group were significantly lower than controls. However, in the 6-hr ischemia group, indexes of both the ischemic insult and ischemia/reperfusion groups were significantly lower than controls. These results demonstrated that bone damage was detected with ischemia at normothermia even after 1 hr; however, this tissue damage was overcome by reperfusion. There was no recovery from damage in bones that had been preserved for more than 6 hr, resulting in irreversible degeneration. Therefore, in clinical vascularized bone grafts, it appears that transplantation should be done within a 3-hr ischemic period for it to be successful.

Animals↗