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Biomedical subjects

H Doi

Publications and source records attributed to H Doi.

At least 109 records · Page 6Linked to original sources

Mechanical properties and corrosion resistance of Ti-6Al-7Nb alloy dental castings.

With the aim of applying a novel titanium alloy, Ti-6Al-7Nb, to a dental casting material, a comprehensive research work was carried out on its characteristics, such as castability, mechanical properties and corrosion resistance in the present study. As a result, Ti-6Al-7Nb alloy exhibited sufficient castability by a dental casting method for titanium alloys and enough mechanical properties for dental application. It is also showed excellent corrosion resistance through an immersion test in 1.0% lactic acid and an anodic polarization test in 0.9% NaCl solution. From these results, it is concluded that this Ti-6Al-7Nb alloy is applicable as a dental material in place of Ti-6Al-4V alloy, which includes cytotoxic vanadium.

Journal Article↗

Influence of aging heat treatment on mechanical properties of biomedical Ti-Zr based ternary alloys containing niobium.

Titanium-zirconium based alloys containing a small amount of niobium were investigated in order to evaluate their possible use as biomedical materials. Zirconium, which belongs to the IVa group, is known to have good corrosion resistance and biocompatibility similar to titanium. As the titanium-zirconium system shows a complete solid solution, a wide variation of alloy design is available and large quantities of solid-solution hardening must be possible. Niobium, having a beta-phase stabilizing effect, was chosen as a ternary element in order to control desirably the microstructure. There have been no reports which suggest its harm to a living body. The alloys containing 2% or 3% niobium showed the highest hardness value after aging heat treatment at 773 K. In contrast to this, no alteration of hardness was seen in specimens aged at 1073 K. Through conventional X-ray diffractometry and in situ X-ray analysis using a hot stage, beta-phase precipitation in the A matrix was identified. From the above results, it is concluded that alloys containing 2%-3% niobium are hopeful candidates for new kinds of biomedical alloys, when they are heat treated under suitable conditions.

Journal Article↗

Structural characterization of a DNA duplex modeled on a DNA:RNA hybrid of the polypurine tract recognized by a reverse transcriptase.

The structure of d(TTAAAAGAAAAGGG):d(CCCTTTTCTTTTAA) has been characterized by NMR. The minor grooves of the two dA-tracts are suggested to be rather narrow, and the portion linking the two dA tracts exhibits a slightly deviated structure from a standard B DNA, in order to maintain the narrowness of the minor groove. The structure of the dG-tract is also slightly deviated. Additionally, specific broadening of resonances is observed for the residues at or near the junction between the dA-tract and the dG-tract, suggesting local structural polymorphology.

Base Sequence↗

Cardiovascular effect of a new 1,5-benzothiazepine derivative TA-993 in anesthetized dogs.

TA-993 is a new 1,5-benzothiazepine derivative having l-cis configuration and shows a potent antiplatelet aggregating action. We studied its cardiovascular effect in anesthetized dogs by using diltiazem as a reference compound. TA-993 (> or = 10 microg/kg, i.v.) significantly increased blood flows of common carotid, brachial, and femoral arteries. The peak of its effect was observed approximately 60 min after the administration, and the peak level was maintained until > or = 300 min after the administration. TA-993 (100 microg/kg, i.v.) slightly increased cardiac output in the same manner. However, TA-993 did not cause any persistent effects on arterial pressure, LVdP/dtmax, or vertebral, coronary, superior mesenteric, and renal blood flows. TA-993 caused concentration-dependent vasorelaxation in the isolated canine femoral artery contracted with 40 mM K+, but its potency was approximately 1/20 that of diltiazem. The increasing action of TA-993 on femoral blood flow was completely inhibited by pretreatment with hexamethonium in anesthetized dogs. These results indicate that TA-993 has a selective increasing action on common carotid, brachial, and femoral blood flows and suggest that the action is mediated by the autonomic nervous system.

Animals↗

Antithrombotic action of TA-993, a new 1,5-benzothiazepine derivative, in a canine model of femoral arterial thrombosis.

TA-993 is a novel 1,5-benzothiazepine derivative of l-cis configuration, having a potent antiplatelet action and an increasing action on femoral blood flow. We evaluated the antithrombotic effect of TA-993 in a canine model of femoral arterial thrombosis. Thrombus was induced by both application of direct anodal current to the femoral artery and partial occlusion of the artery. The partial occlusion by placing an adjustable occluder on the artery and the current application were carried out 40 and 60 min after the intraduodenal administration of drugs, respectively. In control dogs, complete sustained occlusion of the femoral artery due to thrombus occurred 55.4 +/- 9.2 min after the onset of current application. TA-993 (3 and 10 mg/kg) dose-dependently prolonged the time for occlusion. Aspirin (30 mg/kg) also prolonged it. TA-993, 10 mg/kg, significantly inhibited whole-blood aggregation 60 min after the administration with a weaker potency than that of aspirin (30 mg/kg), whereas 3 mg/kg of TA-993 did not. The inhibitory effect of TA-993 (10 mg/kg) on platelet aggregation was maintained for >7 h. Moreover, TA-993 (10 mg/kg) increased femoral blood flow in spite of the partially occluded condition. These results indicate that TA-993 has an antithrombotic effect on femoral arterial thrombosis and suggest that an increasing action on femoral blood flow of TA-993 is more relevant than its antiplatelet action to the antithrombotic effect in this model.

Animals↗

A new operative method for treatment of xanthelasma or xanthoma palpebrarum: microsurgical inverted peeling.

A new operative technique for treatment of xanthelasma or xanthoma palpebrarum was introduced. The merits of this technique are (1) no skin excision with the tumor, (2) making the flap from the skin covering the tumor, (3) no need for donor site, (4) no significant cosmetic problem, and (5) reoperation performed by same procedure. Our new technique is performed under local anesthesia. The skin and tumor are raised together just above the orbicularis oculi muscle like a flap. The tumor is peeled piece by piece from the flap using micro-scissors under a surgical microscope. After tumor enucleation is performed, the skin flap without the tumor is sutured back directly. Our new technique was performed for seven cases of xanthelasma. The recurrence of the tumor was seen only in two cases, which were complicated with hypercholesterolemia. No recurrence was observed after a secondary operation and with the use of anti-hypercholesterolemic drugs. Large xanthelasma can be treated by our new surgical technique without extra skin excision with the best possible cosmetic results.

Aged↗

Biphasic regulation of transcription factor nuclear factor-kappaB activity in human endothelial cells by lysophosphatidylcholine through protein kinase C-mediated pathway.

Lysophosphatidylcholine (lysoPC), which is generated in oxidized LDL (Ox-LDL) and abundantly exists in atherosclerotic arterial walls, has been shown to alter various endothelial functions and induces several endothelial genes expressed in atherosclerotic arterial walls. Nuclear factor-kappa B (NF-kappaB), a pleiotropic transcription factor, plays an important role in regulation of expression of various genes implicated in atherosclerosis. We have previously reported that lysoPC transferred from Ox-LDL to endothelial surface membrane activates endothelial protein kinase C (PKC), leading to modulated endothelial functions. This study was aimed at determining whether lysoPC could modulate activity of transcription factors in cultured human umbilical vein endothelial cells (HUVECs) by using electrophoretic mobility shift assay. LysoPC was found to increase DNA-binding activity of NF-kappaB in HUVECs within 15 minutes, which peaked at 1 to 2 hours and subsequently declined to the baseline level at 6 hours. Lower concentrations (5 to 15 micromol/L) of lysoPC markedly increased NF-kappaB activity, but higher concentration (50 micromol/L) of lysoPC inhibited the activity. Phorbol 12-myristate 13-acetate, a potent activator of PKC, also augmented NF-kappaB activity in HUVECs, mimicking the effects of lysoPC; furthermore, calphostin C and chelerythrine chloride, specific PKC inhibitors, and alpha-tocopherol, a clinically potent PKC inhibitor, suppressed the lysoPC-induced NF-kappaB activation. These results indicate that lysoPC regulates NF-kappaB activity in a biphasic manner dependent on its concentrations and incubation time in human endothelial cells and the endothelial PKC activation may in part be involved in the lysoPC-induced NF-kappaB activation. Thus, the time course and the positive and negative biphasic regulatory actions of lysoPC on NF-kappaB activity in endothelial cells might exhibit a unique effect of lysoPC in arterial walls on the different stages of atherosclerosis.

Cells, Cultured↗

Cardiovascular effects of 1,5-benzothiazepine derivatives having a l-cis and d-cis configuration in anesthetized dogs.

TA-993, a new 1,5-benzothiazepine derivative having a l-cis configuration, has a selective increasing action on limb blood flow, in addition to an antiplatelet aggregating action. The cardiovascular action of TA-993 is quite different from diltiazem, which is a well-known 1,5-benzothiazepine derivative having a d-cis configuration. Therefore, we compared the cardiovascular actions of d-cis and l-cis isomers of TA-993 with those of diltiazem. l-cis-Diltiazem, as well as TA-993, progressively increased femoral, brachial and common carotid blood flow with little change in arterial pressure or vertebral blood flow. However, the peak response to l-cis-diltiazem (20 min after the administration) was observed earlier than that to TA-993 (60 min after the administration). On the other hand, d-cis-TA-993, as well as diltiazem, caused transient hypotension, tachycardia and increases in vertebral, brachial, femoral and common carotid blood flow. Furthermore, their peak effects were observed immediately after the administration. Potency ratios of the vasorelaxing effects of TA-993, l-cis-diltiazem and d-cis-TA-993 to diltiazem in the isolated and K+-contracted canine femoral artery were 0.096, 0.032 and 1.209, respectively. pA2 values for TA-993 and diltiazem against Ca2+-induced contractions in the isolated and K+-depolarized canine saphenous artery were 5.50+/-0.11 and 7.12+/-0.18, respectively. These results indicate that TA-993 shares a common profile with l-cis-diltiazem, and suggest that 1,5-benzothiazepine derivatives of a l-cis configuration are a different class of drug from that of the d-cis configuration.

Anesthesia↗

Synthesis of 11C/13C-labelled prostacyclins.

A one-pot synthesis of (15R)-16-(3-[11C]methylphenyl)-17,18,19, 20-tetranoriso-carbacyclin methyl ester was performed using a palladium-promoted reaction of [11C]methyl iodide with (15R)-16-(3-tri-n-butylstannylphenyl)-17,18,19, 20-tetranorisocarbacyclin methyl ester. The C-15 epimer (15S)-16-(3-[11C]methylphenyl)-17,18,19,20-tetranorisocarbacyclin methyl ester was synthesised in the same way starting from (15S)-16-(3-tributylstannylphenyl)-17,18,19,20-tetranorisocarba cyclin methyl ester. The decay-corrected radiochemical yields were 33-45% based on [11C]methyl iodide produced, and the radiochemical purity of the product was > 95%. The total synthesis time was 35 min, counted from end of radionuclide production to product ready for administration. The 11C-labelled prostacyclin methyl esters were easily hydrolysed using sodium hydroxide affording the 11C-labelled prostacyclin acids in quantitative yields. The stereoisomers (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [11C]methyl ester and (15S)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin [11C]methyl ester were synthesised by esterification using [11C]methyl iodide and the tetrabutylammonium salts of (15R)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid and (15S)-16-(3-methylphenyl)-17,18,19,20-tetranorisocarbacyclin acid, respectively. The decay-corrected radiochemical yields were in the range of 55% counting from [11C]methyl iodide produced, and the radiochemical purity of the product was > 95%. The total synthesis time was 35 min, counting from end of radionuclide production to product ready for administration. Both of these labelling methods can be used for labelling with 13C when (13C)methyl iodide is used. The methods described herein have already proved important since they enable the in vivo use of PET to study the action of prostacyclins in the brain.

Carbon Isotopes↗

[Human immunodeficiency virus and AIDS in terms of reverse transcriptase and molecular evolution].

Human immunodeficiency virus type 1 (HIV-1) evolves rapidly in the host. The computer analysis of the HIV-1 genome has shown that the mutation manner is dependent on oligonucleotide sequences (in particular, six bases long); thus HIV-1 adaptively evolves. The six-base-long interaction between template-primer oligonucleotide and the reverse transcriptase (RT) has been revealed by the crystal structure of RT, in vitro termination assay of plymerization, and hydroxyl radical footprint analysis. It has been thought that AIDS is caused by the large numbers of HIV-1 quasispecies yielded by the adaptive and rapid evolution in the host. However, the slow evolution and the high levels of viral RNA in the progressive HIV-1 infected individuals (progressives) were recently reported; in contrast, the adaptive and rapid evolution and the low viral-RNA levels were reported in the non-progressives. This suggests that the physiological environment, e.g. pH and dNTP balance, in which RT works in the progressives is different from that in the non-progressives.

Acquired Immunodeficiency Syndrome↗

Salicylic acid-induced lipid peroxidation in rat liver microsomes.

Rat liver microsomes (1 mg protein/ml) were incubated at 37 degrees C with non-steroidal anti-inflammatory drug, salicylic acid (5 mM) in the presence of 0.2 mM NADPH. The amounts of thiobarbituric acid reactive-substances (TBARS) were increased remarkably by the incubation for 30 min. TBARS formation was dependent on salicylic acid concentration. Salicylic acid-induced lipid peroxidation was not observed in the absence of NADPH. It was also inhibited by the presence of cytochrome P450 inhibitor, SKF-525A. The singlet oxygen's scavengers such as histidine suppressed salicylic acid-induced lipid peroxidation. These results suggested that salicylic acid-induced lipid peroxidation was coupled with the metabolism through cytochrome P450 in rat liver microsomes. The singlet oxygen may be involved in the reaction.

Animals↗

[Coronary angiography provides considerable in vivo pathophysiological information on coronary artery disease].

Coronary cineangiography (CAG) has various limitations and pitfalls, but is widely accepted for evaluating coronary circulation. The interpretation of CAG focuses mainly on the extent and location of coronary artery disease. However, CAG can also provide considerable and varied in vivo pathophysiological information on coronary artery disease as follows: Certain in vivo angiographic coronary morphologies are indicative of histological findings, such as ruptured atheromatous plaque with/without overlying thrombus. Such morphologies are commonly found in patent ischemia- or infarct-related arteries of patients with acute coronary events in both the acute phase and one month after standard medication, and the diseased portion with the morphology is highly specific to the culprit site. The rupture of plaque and overlaid thrombus is just as important in patients with acute coronary events who survive as in patients who die. Diseased sites with complex lesions are prone to progress toward clinical ischemic episodes. The severity of coronary narrowing immediately after acute coronary events does not influence later left ventricular function if antegrade coronary blood flow without distal filling delay is preserved. Coronary stenosis induced by plaque rupture and superimposed thrombus is likely to improve or disappear with time and/or anticoagulant administration with/without antiplatelet therapy. Such information derived from CAG may improve the understanding and suggest optimal therapeutic strategies of coronary artery disease for individual patients.

Coronary Angiography↗

Asymmetrical DNA replication promotes evolution: disparity theory of evolution.

Heredity is guaranteed by faithful DNA replication whereas evolution depends upon errors accompanying DNA replication. This contradiction existing between heredity and evolution cannot be resolved in an individual organism, but only in terms of a population, in that a delicate balance exists between wild type and variants in a population which is necessary for the survival of the species. Namely, there seems to be a key in the mechanism of DNA replication to solve some problems of evolution. DNA is replicated semiconservatively using the leading and discontinuous lagging strands. According to our 'disparity theory of evolution', the existence of a sufficient fidelity difference between the leading and lagging strands is advantageous in terms of evolution, because the diversity of genotypes is enlarged but genotypes that have occurred in the past are guaranteed. In theory, by artificially increasing the fidelity difference between the leading and lagging strand ('disparity mutator'), evolution is accelerated while avoiding the extinction of the population. Using a disparity mutator, we should be able to improve living things, including multicellular organisms, within constrained conditions. A double-stranded algorithm, which mimics the structure and replication manner of DNA, is promising for solving optimization problems.

Animals↗

Levodopa effective parkinsonism associated with aqueductal stenosis: a case report and review of the literature.

A case of aqueductal stenosis (AS) associated with marked parkinsonism is described. A ventriculoperitoneal (V-P) shunt was performed in an 18-year-old female because of hydrocephalus associated with non-neoplastic aqueductal stenosis. The patient developed acute parkinsonism with Parinaud's sign after the shunt revision. She had a marked response to levodopa and the parkinsonism improved. Subsequently, levodopa therapy was gradually discontinued without any manifestation of parkinsonism. The pathophysiology of this type of parkinsonism probably involved presynaptic dopaminergic dysfunction. However, the etiology of this complication has not been confirmed.

Adolescent↗

Presence of B cell progenitors in the thymus.

We characterize B cell progenitors in the thymus. Although mature thymic B cells are surface Ig+, B220(high), but CD43-, B cell progenitors in the thymus were found to be slg-, B220(med), and CD43+. Most progenitors showed rearranged Ig D-J and V-D-J patterns when DNA from sorted B cell progenitors was amplified by PCR, blotted, and probed. When B cell progenitors were purified from the thymus and injected intrathymically into Ig heavy chain (Igh) allotype-disparate recipients, B cells bearing donor-type Igh6 were detected in the thymus but not in the periphery. Thymic B cells generated from these progenitors were CD5+ cells, although there was a broad range of expression of CD5 molecules. Furthermore, B cells purified from thymus that had been inoculated with B cell progenitors were able to differentiate into Ab-forming cells under the influence of CD40 ligand plus IL-10, and secreted IgM with donor Igh6 allotype. We thus clarified the existence of B cell progenitors in the thymus and also characterized the surface markers and their developmental functions.

Animals↗

Pluripotent hemopoietic stem cells are c-kit<low.

Pluripotent hemopoietic stem cells (P-HSCs) were thought to be c-kit+, but recent reports indicate that they are c-kit(low). In the present report, we provide evidence using Ly5 congenic mice that P-HSCs are c-kit(<low). Lineage-negative (Lin-)/CD71- cells among bone marrow cells (BMCs) from C57BL/6 Ly5.1 mice were separated into major histocompatibility complex class I(high) (class I(high))/c-kit(low) and class I(high)/ c-kit(<low) populations. Each population (500 cells) was transplanted into lethally (9.0 Gy) irradiated C57BL/6 Ly5.2 congenic mice along with Ly5.2 (2 x 10(5)) compromised cells. Donor-derived Ly5.1+ cells were detected 6 months after transplantation in primary recipients reconstituted with either class I(high)/c-kit(low) or class I(high)/c-kit(<low) cells. BMCs (1 x 10(6)) from the primary recipients were further transplanted into secondary recipients (Ly5.2 mice) to assess their long term repopulating activity. Six months after bone marrow transplantation, Ly5.1+ cells in all lineages were detected only in secondary recipients that had been given BMCs from the primary recipients reconstituted with class I(high)/c-kit(<low) cells but not in cells that were class I(high)/c-kit(low). When the BMCs (1 x 10(6)) of these secondary recipients were further transplanted into tertiary recipients, all tertiary recipients that had been given BMCs from the secondary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(low) cells died within 10 days whereas all six tertiary recipients originally reconstituted with Lin-/CD71-/class I(high)/c-kit(<low) cells showed donor (Ly5.1+)-derived cells in their peripheral blood. In the single tertiary recipient that was killed, donor-derived T cells, B cells, macrophages, and granulocytes also were detected in several major hematolymphoid organs. The remaining five mice continue to survive more than 6 months after the tertiary bone marrow transplantation.

Animals↗

Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril.

The aim of this study was to examine the effects of the water soluble component of cigarette smoke extract (CSE) on endothelium-dependent relaxation (EDR) of isolated rabbit aortas. The incubation with CSE was found to inhibit EDR in a dose-dependent manner. Co-incubation of the aortic strips with superoxide dismutase (SOD), N-acetylcysteine, glutathione or dimethyl sulfoxide (DMSO), free radical scavengers, attenuated the CSE-induced inhibition of the arterial relaxation. Co-incubation of the strips with captopril (3 mM), an angiotensin converting enzyme inhibitor, also attenuated CSE-induced impairment of vasorelaxation. In parallel experiments using cultured human endothelial cells, CSE suppressed endothelial release of NOx, stable metabolites of nitric oxide (NO). SOD, DMSO and captopril attenuated the suppression of NO production by CSE in association with reduction of free radicals, superoxide anions and hydroxyl radicals, in CSE solution. Neither lactate dehydrogenase release from the cultured endothelial cells nor cell death estimated by trypan blue exclusion test was found after the incubation of the cultured endothelial cells with CSE. The results indicate that free radicals in CSE induce the impairment of EDR, which may be partly due to suppression of NO production and is not due to non-specific cytotoxicity by CSE. Captopril attenuates CSE-induced endothelial dysfunction partly through scavenging free radicals.

Acetylcysteine↗

Liver transplantation for severe hypoxemia caused by patent ductus venosus.

The authors describe the case of a 9-year-old girl who underwent liver transplantation because she suffered from severe hypoxemia caused by patent ductus venosus (PDV). Generally, severe hypoxemia (PaO2 < 50 mm Hg in room air or < 300 mm Hg in pure oxygen) is not an indication for liver transplantation because the hypoxemia may not be improved, and may lead to a fatal outcome. PDV, which is associated with mild liver dysfunction, is not an indication for liver transplantation by itself. But in our patient, most of the mesenteric venous flow directly entered the systemic circulation through the PDV just like the portosystemic shunt, and this caused the pulmonary arteriovenous shunt and hypoxemia. Thus, the authors operated on the patient in an attempt to restore her pulmonary function. Nitric oxide (10 to 20 ppm) was added to the inhaled gas to dilate the functional pulmonary capillaries and to deliver sufficient oxygen after the transplantation. Although the patient suffered various complications after the operation, the final results were excellent.

Angiography, Digital Subtraction↗