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Biomedical subjects

Y Takakura

Publications and source records attributed to Y Takakura.

At least 73 records · Page 4Linked to original sources
PubMed2000

Precise anatomic configuration changes in the first ray of the hallux valgus foot.

To detect precise anatomical configuration of the first ray in feet with hallux valgus, a two-dimensional coordinate system was devised for evaluation of a weight-bearing dorsoplantar radiograph. The radiographs, taken from 229 feet of 114 patients with symptomatic hallux valgus and 94 normal feet, were investigated. A comparative study showed the first metatarsal head of a foot with hallux valgus was located on the medial side of that of the normal foot and the base of the proximal phalanx of the hallux valgus foot was located on the same point of that of the normal foot. Lateral translation of the base of the proximal phalanx occurred only in cases with overlap toes. Our study shows that subluxation of the metatarsophalangeal joint in hallux valgus is primarily caused by metatarsus primus varus. This study indicated that first metatarsal osteotomies should be given the first priority in consideration for bunion surgery, because these procedures could move the first metatarsal heads laterally in a more normal position.

Adolescent↗
PubMed2000

Age-dependent decreases of phosphorus and magnesium in human Achilles' tendons.

To elucidate changes of human tendons with aging, the authors studied age-related changes of elements in human Achilles' tendons by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. It was found that the content of calcium increased progressively with aging in the Achilles' tendons, whereas the contents of phosphorus and magnesium decreased gradually with aging. The previous investigations demonstrated that the content of calcium and phosphorus increased progressively with aging in most, but not all, human tissues, except for the bones. In ligaments, such as the anterior cruciate ligament and the ligament of the head of the femur, which are histologically similar to the Achilles' tendon, it was previously found that both the contents of calcium and phosphorus increased with aging in the ligaments. It should be noted that the content of phosphorus in the Achilles' tendons decreased during the aging process. In addition, it was found that there was a very high direct correlation between phosphorus and magnesium contents in the tendons, but not between calcium and phosphorus contents.

Achilles Tendon↗
PubMed2000

Accumulation of calcium and phosphorus in the mitral valve in comparison with the abdominal aorta and the scaphoid bone.

To clarify why calcification of the mitral valve occurred, the authors chose the abdominal aorta and the scaphoid bone among many arteries and bones, and they studied both relationships in element contents between the mitral valve and the abdominal aorta and between the mitral valve and the scaphoid bone. The subjects consisted of 11 men and 8 women, ranging in age from 52 to 96 yr. The accumulation of calcium and phosphorus occurred progressively with aging in the mitral valve, whereas it became the highest in the sixties in the abdominal aorta and did not increase thereafter. The accumulation of calcium and phosphorus occurred in the abdominal aorta earlier than the thoracic aorta, in which it became remarkable in the seventies. It should be noted that in regard to the accumulation of calcium and phosphorus, no significant correlations were found between the mitral valve and the abdominal aorta. It is suggested that calcification of the abdominal aorta is not essentially accompanied by calcification of the mitral valve. The scaphoid bone was chosen among many bones consisting mainly of spongy bone and the relationship was examined between the calcium content in the mitral valve and the bone mineral density of the scaphoid bone. It was found that there was a low relationship between them. Therefore, it is suggested that a part of the surplus calcium released from bones is deposited in the mitral valve.

Aged↗
PubMed2000

Treatment of extrinsic flexion deformity of the toes associated with previous removal of a vascularized fibular graft.

BACKGROUND: Complications from vascularized fibular bone-grafting are infrequent. We saw six patients who had a painful flexion deformity of the great and lesser toes after a free vascularized fibular graft had been obtained from the ipsilateral leg. In this report, we discuss our management of these patients. METHODS: Painful flexion deformity of the toes that had developed in six adults after removal of a free vascularized fibular graft was treated by cutting of the flexor hallucis longus alone in three patients, by lengthening of the flexor hallucis longus alone in one, and by cutting of both the flexor hallucis longus and the flexor digitorum longus in two. RESULTS: After an average duration of follow-up of six years and eleven months, the flexion deformity of the great and lesser toes had decreased or disappeared, leading to improved or full extension of the digits. Preoperative and postoperative measurements of muscle strength for plantar flexion of the interphalangeal joints did not change appreciably. CONCLUSIONS: Cutting or lengthening of the flexor hallucis longus behind the ankle provides an adequate release of digital flexion deformities that occur after removal of a vascularized fibular bone graft.

Adult↗
PubMed2000

Pharmacokinetics and in vivo gene transfer of plasmid DNA complexed with mannosylated poly(L-lysine) in mice.

To achieve mannose receptor-mediated, cell-specific, in vivo gene transfer by intravenous injection of plasmid DNA, mannosylated poly(L-lysine) (Man-PLL) was synthesized as a carrier molecule, and mixed with a plasmid DNA encoding chloramphenicol acetyltransferase (CAT) gene to form DNA/Man-PLL complex. The particle size and zeta potential of DNA/Man-PLL (prepared at 1:0.7 on a weight basis) were determined to be 220 nm and +12 mV, respectively. The pharmacokinetics of the DNA/Man-PLL complex was assessed in mice using 32P-labeled DNA ([32P]DNA). After intravenous injection of [32P]DNA/Man-PLL, the radioactivity in plasma fell rapidly and was recovered mainly in the liver nonparenchymal cells. The amount in the liver reached more than 80% of the dose. Radioactivity observed in kidney, lung, and spleen was very low compared to that in the liver. Then, the in vivo gene expression after intravenous injection of DNA/Man-PLL was examined by a CAT assay. Highest CAT activity was detected in the liver, but no activity was detected in the lung, kidney, and spleen. These results clearly indicate that a cell-specific gene delivery system can be developed by regulating the biodistribution of DNA/carrier complex through the control of its physicochemical properties.

Animals↗
PubMed2000

Effect of cationic liposomes on intracellular trafficking and efficacy of antisense oligonucleotides in mouse peritoneal macrophages.

We have investigated the intracellular fate and antisense effect of oligonucleotide/cationic liposome complexes using phosphorothioate oligonucleotides (S-Oligo) targeted to inducible nitric oxide synthase in mouse peritoneal macrophages. Confocal laser microscopic analysis revealed that, after application of fluorescein isothiocyanate (FITC)-labeled S-Oligo alone, the intracellular localization of fluorescence exhibited a punctate pattern in the cytoplasm, suggesting that the oligonucleotides were mainly confined to the endosomal and/or lysosomal compartments. In the case of complexation with Lipofectin and DMRIE-C liposomes, cellular uptake of FITC-S-Oligo was not greatly enhanced and the fluorescence localization in the cells was similar to that of FITC-S-Oligo alone. LipofectAMINE slightly enhanced cellular uptake of FITC-S-Oligo; however, the intracellular localization profile of FITC-S-Oligo remained largely unchanged. The antisense effect was slightly enhanced by LipofectAMINE under only very limited experimental conditions. It was concluded that cationic liposomes are not a potential carrier for S-Oligo in peritoneal macrophages because of their inability to promote the release of S-Oligo from the endosomal compartments to the cytosol over a non-toxic concentration range.

Animals↗
PubMed2000

Design of polymeric prodrugs of PGE1 for cell-specific hepatic targeting.

Based on the relationship between in vivo disposition of macromolecules and their physicochemical and biological characteristics obtained through clearance concept-based pharmacokinetic analysis, polymeric prodrugs of prostaglandin E1 (PGE1) were designed stepwise and evaluated on their targeting and therapeutic efficiencies. Although galactosylated poly-L-glutamic acid with a ethylene diamine (ED) spacer (Gal-ED-PLGA) showed good targeting efficacy in mice, its PGE1 conjugate synthesized by the carbonyldiimidazole method failed to show therapeutic effects probably due to inactivation of PGE1 during conjugation and lack of release in the tissue. In order to overcome these problems, PGE1 was conjugated to galactosylated poly-(L-glutamic acid) hydrazide (Gal-HZ-PLGA) via hydrazone bond. The PGE1-Gal-HZ-PLGA conjugate labeled with [111In] or [3H]PGE1 rapidly accumulated in the liver parenchymal cells after intravenous injection. In addition, PGE1 conjugate effectively inhibited the increase of GPT level in plasma, while free PGE1 indicated no therapeutic efficacy even at more than ten times higher doses, in carbon tetrachloride-induced hepatitis mice. These findings suggest potentials of polymeric targeting systems of PGE1 to hepatocyte utilizing galactose recognition.

Acute Disease↗
PubMed1999

Design of polymeric prodrugs of prostaglandin E(1) having galactose residue for hepatocyte targeting.

Based on the relationship between in vivo disposition of macromolecules and their physicochemical and biological characteristics obtained through clearance concept-based pharmacokinetic analysis, polymeric prodrugs of prostaglandin E(1)(PGE(1)) were designed stepwise and evaluated on their targeting and therapeutic efficiencies. First poly-L-lysine (PLL) and poly-L-glutamic acid (PLGA) with an ethylenediamine (ED) spacer were modified with 2-imino-2-methoxyethyl 1-thiogalactoside to obtain galactosylated derivatives. After intravenous injection in mice, Gal-ED-PLGA was selectively taken up by the liver parenchymal cells via receptor-mediated endocytosis, while Gal-PLL accumulated in the liver as well as PLL mostly due to electrostatic interaction. Although Gal-ED-PLGA showed good targeting efficacy, its PGE(1) conjugate synthesized with activated PGE(1) by carbonyldiimidazole method failed to show therapeutic effects probably due to inactivation of PGE(1) during conjugation and lack of release in the tissue. In order to overcome these problems, we next conjugated PGE(1) to galactosylated poly-(L-glutamic acid) hydrazide (Gal-HZ-PLGA) in which PGE(1) was easily coupled to Gal-HZ-PLGA via a hydrazone bond in weak acidic solution (pH 5) at room temperature. The PGE(1)-Gal-HZ-PLGA conjugate labeled with [(111)In] or [(3)H]PGE(1) rapidly accumulated in the liver parenchymal cells. In addition, the PGE(1) conjugate effectively inhibited the increase of the GPT level in plasma, while free PGE(1) indicated no therapeutic efficacy even at more than ten times higher doses, in carbon tetrachloride-induced hepatitis mice. These findings suggest potentials of polymeric targeting systems of PGE(1) to hepatocyte utilizing galactose recognition.

Alprostadil↗
PubMed1999

Interaction of polystyrene microspheres with liver cells: roles of membrane receptors and serum proteins.

Our previous studies have demonstrated that serum would play an important role in the hepatic disposition of polystyrene microspheres (MS) and that complement C3 should be involved as the serum opsonin. In this study, we tried to identify the entity of other serum opsonins and dysopsonin for the hepatic uptake of MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion studies using a recirculation procedure in rats. Pretreatment of the liver by trypsin significantly suppressed the serum-dependent hepatic uptake of both MSs, suggesting that some protein components on the cell surface should be necessary for the serum-dependent phagocytosis of MSs. Pretreatment of the serum by the anti-fibronectin antibody resulted in a significant reduction in the hepatic disposition of MS-500 (49% of control), suggesting that fibronectin should also work as the opsonin for the hepatic uptake of MS-500. The hepatic disposition of both MSs in the presence of serum was inhibited by the addition of N-acetylgalactosamine into the perfusate, suggesting the possible involvement of lectin in the serum-dependent hepatic uptake of MSs. Furthermore, a more intensive hepatic disposition of MSs was observed in the presence of plasma compared with that in the presence of serum in the perfusate, suggesting the possible involvement of blood coagulation factors, such as fibrinogen, as the opsonin in the hepatic disposition of MSs.

Animals↗
PubMed1999

Mechanisms of hepatic disposition of polystyrene microspheres in rats: effects of serum depend on the sizes of microspheres.

To study the mechanisms of the hepatic disposition of polystyrene microspheres (MS), effects of serum on their hepatic disposition characteristics were investigated for MSs with particle sizes of 50 nm (MS-50) and 500 nm (MS-500) by isolated liver perfusion experiments. It was revealed that serum in the perfusate inhibited and promoted the hepatic disposition of MS-50 and MS-500 at 37 degrees C, respectively. However, pre-heating at 56 degrees C or pre-treatment with anti-C3 antibody of serum reduced the promotive effect of serum on the hepatic uptake of MS-500, suggesting that the complement system should be involved as opsonins for the hepatic uptake of MS-500. Hepatic disposition of both MSs at 4 degrees C was reduced by the addition of serum into the perfusate, which could be ascribed to the reduction of the surface hydrophobicity of MSs due to the adsorption of serum proteins onto the surface of MSs and to resultant decrease in non-specific disposition to the liver. From these results, serum was found to function both as the opsonin to enhance the hepatic uptake of MSs and as the inhibitor by reducing non-specific interaction between MSs and the plasma membrane. Whether serum promotes or inhibits the hepatic disposition of MSs would be dependent on the particle sizes of MSs.

Animals↗
PubMed1999

Hepatic uptake of polystyrene microspheres in rats: effect of particle size on intrahepatic distribution.

The in vivo disposition of polystyrene microsphere (MS) with the particle size of 50 nm (MS-50) or 500 nm (MS-500) was characterized after intravenous administration to rats. A rapid elimination from systemic circulation was observed for both MSs. Tissue distribution of MS-50 and MS-500 at 1 h after intravenous injection indicated that both MSs were exclusively distributed to liver and that small but significant amounts of MS-50 and MS-500 were also distributed to lung and spleen, respectively. To investigate the intrahepatic distribution of MS, liver was separated into liver parenchymal cells (PC) and non-parenchymal cells (NPC) at 1 or 6 h after intravenous administration. The contribution of each cell fraction was dependent on both the size of MS and the time after administration. Furthermore, by separating the NPC into endothelial cells and Kupffer cells using a centrifugal elutriation method, their contribution was also evaluated. For both MSs, Kupffer cells were recognized to be mostly responsible for the hepatic uptake, although a significant amount of MS-50 (about 28% of total uptake) was taken up by PC. On the other hand, there was little contribution of PC (about 5%) to the hepatic uptake of MS-500. The endothelial cells were contributed larger to the uptake of MS-500 (about 24%) than that of MS-50 (13%).

Animals↗
PubMed1999

Liver uptake and hepato-biliary transfer of galactosylated proteins in rats are determined by the extent of galactosylation.

The effect of molecular mass and surface density of galactose residues on hepatic uptake and subsequent biliary excretion of galactosylated proteins was investigated in rats. Several proteins with different molecular weights (15-70 kDa) and different numbers of galactose units were synthesized and radiolabeled with 111In. Galactosylated proteins were administered i.v. to anaesthetized rats and samples of plasma and bile were collected for 3 h. Liver was harvested at the end of the experiments and the radioactivity of all samples was measured. Galactosylated proteins accumulated primarily in the liver and 2-10% of the administered dose appeared in the bile, mainly in undegraded form. The hepatic uptake clearance (Cl liver) and biliary excretion rate constant (kbile) of galactosylated proteins were calculated. No direct effect of molecular weight was observed, however, on increasing the galactose density, Cl liver increased from about 4 to 400 ml/h whereas kbile gradually decreased from about 0.057 to 0.007 (h-1). In conclusion, both hepatic uptake and biliary excretion of galactosylated proteins were found to be affected by the extent of galactosylation.

Animals↗
PubMed1999

Pharmacokinetics and disposition characteristics of recombinant decorin after intravenous injection into mice.

The pharmacokinetics and disposition characteristics of recombinant decorin after intravenous administration were investigated in mice. Following bolus injection of 111In-labeled decorin at doses of 0.02 and 0.1 mg/kg, radioactivity rapidly disappeared from the circulation and approximately 70% of the dose accumulated in liver within 10 min. 111In-labeled decorin was preferentially localized in hepatic nonparenchymal cells. At a higher dose of 1 mg/kg, clearance from the circulation and hepatic uptake of [111In]decorin were slower than at lower doses. Both the accumulation in other tissues and urinary excretion of [111In]decorin were 5% or less. Pharmacokinetic analysis demonstrated that hepatic uptake clearance was large and accounted almost completely for total body clearance; in addition the clearance values decreased as the dose increased, suggesting that the hepatic uptake of decorin is mediated by a specific mechanism which becomes saturated at higher doses. In competitive inhibition experiments, hepatic uptake of 111In-labeled decorin was partially inhibited (about 20-30%) by several sulfated glycans such as glycosaminoglycans and dextran sulfate and by mannosylated bovine serum albumin (BSA), mannan and mannose to a lesser extent (about 10%). On the other hand, polyinosinic acid, polycytidylic acid and succinylated BSA were ineffective, suggesting that the scavenger receptor for polyanions in the liver is not involved in the hepatic uptake of decorin. A basic protein, protamine, and a ligand of the apoE receptor, lactoferrin, also had no effect. Taken together, the present results have demonstrated that recombinant decorin is rapidly eliminated from the blood circulation through extensive uptake by the liver, primarily by the nonparenchymal cells, following systemic administration. The sugar structure and mannose residue in decorin have also been suggested to play an important role in the hepatic uptake of decorin. These findings provide useful information for the development of decorin as a therapeutic agent.

Animals↗
PubMed1999

Stimulation side-dependent asymmetrical secretion of poly I:poly C-induced interferon-beta from polarized epithelial cell lines.

Mode of secretion of poly I:poly C-induced IFN was examined using epithelial cell lines in a bicameral culture system. Although the cell lines formed a tight cell sheet and produced IFN-beta following poly I:poly C treatment in spite of its application to the upper or lower compartment, IFN secretion differed between the apical and basolateral cell membranes. When poly I:poly C was applied to the upper compartment, IFN was secreted predominantly from the apical membrane. Inversely, poly I:poly C applied to the lower compartment caused preferential IFN secretion from the basolateral membrane. These results suggest that in epithelial cells poly I:poly C stimulation induces intracellular membrane traffic toward the stimulation side.

Animals↗
PubMed1999

Synthesis and pharmacokinetics of a novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate.

A novel macromolecular prodrug of Tacrolimus (FK506), FK506-dextran conjugate, was developed and its physico-chemical, biological and pharmacokinetic characteristics were studied. The conjugate was estimated to contain 0.45% of FK506 and the coupling molar ratio was approximately 1:1 (dextran-FK-506). Adsorption experiments using ion exchangers indicated that FK506-dextran conjugate acted as a weakly negatively charged macromolecule. Low molecular weight radioactive compound(s), which was eluted in the same fractions as [(3)H]FK506, was released from [(3)H]FK506-dextran conjugate by chemical hydrolysis with a half-life of 150 h in phosphate buffer. In vitro immunosuppressive activity of the conjugate, as assessed by the rat lymphocyte stimulation test, was almost comparable to that of free FK506, suggesting that biologically active FK506 could be liberated from the conjugate. In vitro biodistribution studies demonstrated that conjugation with the dextran derivative dramatically changed the pharmacokinetic properties of FK506 after intravenous injection in rats. AUC of the FK506-dextran conjugate was almost 2000 times higher than that of free FK506 and organ uptake clearances of the conjugate were significantly smaller than those of the free drug. Thus, the present study has demonstrated that the FK506-dextran conjugate behaves as a prodrug of FK506 with an extended blood circulating time and can be expected to have an improved therapeutic potency.

Animals↗
PubMed1999

Age-related changes of elements in human anterior cruciate ligaments and ligamenta capitum femorum.

To elucidate compositional changes of human ligaments by aging, the content of elements in anterior cruciate ligaments (ACLs) and ligamenta capitum femorum (LCFs) was analyzed by inductively coupled plasma-atomic emission spectrometry. The subjects consisted of 11 men and 7 women, ranging from 59 to 91 yr of age. With regard to the content of elements, the content of sulfur and iron was significantly higher in the LCFs than in the ACLs. It was found in the ACLs that the content of sulfur decreased gradually with aging, whereas the content of calcium, phosphorus, and magnesium increased progressively with aging. On the other hand, it was found in the LCFs that the content of magnesium decreased gradually with aging, where as the content of phosphorus increased progressively with aging. The common finding that the content of phosphorus increased with aging, but the content of iron decreased, was obtained in the ACL and LCF. Regarding sexual difference, it was found in both the ACLs and LCFs that the content of phosphorus was higher in women's ligaments than in men's.

Aged↗
PubMed1999

Neurohistology of the sinus tarsi and sinus tarsi syndrome.

The purpose of this study was to clarify the neural anatomy of the sinus tarsi. The nerve endings of the synovium in the sinus tarsi were examined. The synovial membrane in the sinus tarsi was excised in 20 patients with sinus tarsi syndrome (20 feet) and in 2 feet from subjects without symptoms (controls). In 15 of the 20 patients and the two controls, the excised synovial membrane was studied histologically with staining by a modified Gairns gold chloride method. Numerous neural elements were observed in the sinus tarsi in all examined synovium. There were abundant free nerve endings and three types of mechanoreceptors: Pacinian corpuscles, Golgi corpuscles, and Ruffini corpuscles. Macroscopic observation and histological examination, using hematoxylin and eosin, in the other 5 patients revealed chronic synovitis in the sinus tarsi. Our findings suggest that the sinus tarsi is not only a talocalcaneal joint space but a source of nociceptive and proprioceptive information on the movement of the foot and ankle. Sinus tarsi syndrome may result from disorders of nociception and proprioception in the foot.

Adolescent↗