Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 37 records · Page 2Linked to original sources

PubMed2001

Behavior of plastid nucleoids during male gametogenesis in Plumbago auriculata.

We characterized the behavior of plastid (pt) and mitochondrial (mt) nucleoids during male gametogenesis in Plumbago auriculata in three dimensions. The behavior of pt-nucleoids and mt-nucleoids differed throughout male gametogenesis. Pt-nucleoids were distributed in a characteristic manner in three stages: in the early microspore, pt-nucleoids assemble around cell nucleus; in the mid-generative cell, pt-nucleoids gather at the internal side of the pollen; in the late-generative cell, pt-nucleoids aggregation turns its pole to the external side of the pollen. We also studied organelle nucleoids in the egg and the central cell by a method in which semi-thick sections of resin-embedded anthers and ovaries were observed by confocal laser scanning microscopy. The number of pt-nucleoids in the sperm cell did not differ significantly from that in the egg. These results suggest that the behavior of DNA-containing organelles is regulated strictly during male gametogenesis in P. auriculata, and that a biparental inheritance of plastids in the Plumbago embryo is more favored than was previously thought.

Cell Nucleus↗

PubMed2001

1alpha-Hydroxyvitamin D3 suppresses trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells after ovariectomy in mice.

To test the hypothesis that 1alpha-hydroxyvitamin D3 (1alpha(OH)D3) suppresses bone resorption after ovariectomy (ovx) by inhibiting osteoclastogenic potential in bone marrow cells, the bilateral tibiae of ddY mice, 8 weeks of age, subjected to ovx were obtained. 1alpha(OH)D3, at doses of 0, 0.2 (low dose), or 0.4 microg/kg body weight (high dose), was administered orally by canula three times a week for 2 or 6 weeks. Histomorphometric analysis of the proximal tibiae revealed that 1alpha(OH)D3 administration had no significant effect on trabecular bone volume of ovx limbs, which was reduced after ovx. The bone formation rate, increased by ovx, was significantly decreased by the administration of high-dose 1alpha(OH)D3. The ovx-induced increases in osteoclast number and surface at 2 weeks postsurgery were suppressed by the administration of high-dose 1alpha(OH)D3. With regard to bone marrow cells, the number of nonadherent cells per tibia obtained from ovx limbs increased, and this increase was suppressed by the administration of low- and high-dose 1alpha(OH)D3. The formation of mineralized nodules in marrow cultures obtained from ovx limbs was increased after surgery and unaltered by 1alpha(OH)D3 administration. The number of osteoclast-like multinucleated cells obtained from ovx limbs was reduced by low- and high-dose 1alpha(OH)D3 administration alike. The number of colony forming units-fibroblast and the number of colony forming units for granulocytes and macrophages was unaltered by ovx or the administration of 1alpha(OH)D3. The present study clearly demonstrates that high-dose 1alpha(OH)D3 suppresses osteoclast numbers and surface after ovx. The inhibitory effects of low- and high-dose 1alpha(OH)D3 on bone marrow cells after ovx were marked in the differentiation from osteoclast precursors to mature osteoclasts. Administration of 1alpha(OH)D3 suppressed ovx-promoted trabecular bone resorption by inhibiting osteoclastogenic potential in bone marrow cells.

Alkaline Phosphatase↗

PubMed2001

Sequential changes in transforming growth factor (TGF)-beta1 concentration in synovial fluid and mRNA expression of TGF-beta1 receptors in chondrocytes after immobilization of rabbit knees.

We have previously reported that a combination of transforming growth factor (TGF)-beta1 and basic fibroblast growth factor (bFGF) synergistically increases the proliferation of chondrocytes obtained from knee joint immobilized for 7-14 days in male Japanese white rabbits. In the present study, we performed experiments with chondrocytes and syn ovial fluid obtained from rabbit knees immobilized for 0-42 days, to clarify the sequential changes in TGF-beta1 and bFGF concentrations in synovial fluid and the mRNA expression of TGF-beta1 receptor type I (RI) and II (RII) in chondrocytes after immobilization. The combination of TGF-beta1 and bFGF had a synergistic effect on the proliferation of chondrocytes obtained from knee joints immobilized for 7-14 days. The concentration of TGF-beta1 in synovial fluid was significantly higher (up to 3.6-fold) at 7-28 days after immobilization compared with that at 2 days. The mRNA for RI and RII was expressed during the whole immobilization period. The con centration of bFGF was kept at the same level at 2-7 days after immobilization, and gradually decreased thereafter. In the early stages of degenerated cartilage, up to 14 days after immobilization, the concentrations of both TGF-beta1 and bFGF were higher in the synovial fluid and mRNA expression of TGF-beta1 receptors in chondrocytes was kept.

Activin Receptors, Type I↗

PubMed2001

Confinement of surface state electrons on Cu and Au field emitters.

Field-emission images of clean Cu and Au emitters show a peculiar halo-like ring centered at the [1 1 1] pole. Typical diameter and width of the ring are approximately 10 nm and approximately 2 nm, respectively. Since we found no geometrical features around the [1 1 1] pole that gives rise to such a ring pattern, we interpreted the ring pattern as representing enhanced emission from an annular terrace that resonantly confines surface electrons. A simple analysis shows that the observed ring pattern appears at a terrace whose width nearly matches the confinement condition.

Journal Article↗

PubMed2001

Effects of gastrointestinal stimulant and suppressant pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic.

The effects of pretreatment with the gastrointestinal stimulant domperidone and the suppressant scopolamine butylbromide on the absorption of AS-924, a novel prodrug-type cephem antibiotic, were investigated in six healthy adult male volunteers by a cross-over method. The T(max) of ceftizoxime (CTIZ), the active moiety of AS-924, was slightly prolonged by scopolamine butylbromide (T(max)=1.8 vs. 1.5 h for the group without pretreatment). However, there were no significant differences in pharmacokinetic parameters including T(max), cumulative urinary excretion rates of CTIZ and cumulative urinary excretion rates of pivaloylcarnitine for 12 h after the dosing between the pretreated and control groups. Domperidone did not affect the absorption of AS-924.

Adult↗

PubMed2001

Effects of food intake and age on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic. Comparison with cefpodoxime proxetil.

The effects of food intake and age on intestinal absorption of AS-924, a novel prodrug-type cephem antibiotic, were examined in 16 healthy adult volunteers (eight young volunteers and eight elderly volunteers) by the cross-over method, using cefpodoxime proxetil (CPOD-PR) as the control drug. The gastrointestinal absorption of AS-924 and CPOD-PR was increased slightly by food intake and the extent of increase was slightly greater after administration of CPOD-PR. The absorption of AS-924 was not affected by age, whereas intestinal absorption of CPOD-PR increased with age. In conclusion, these results confirmed that AS-924 has the unique characteristics as a novel prodrug and that its absorption is less likely to be affected by food intake and age.

Administration, Oral↗

PubMed2001

AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity.

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.

Administration, Oral↗

PubMed2001

Effect of antacid pretreatment on the pharmacokinetics of AS-924, a novel ester-type cephem antibiotic--comparison with cefteram-pivoxil.

The effect of pretreatment with ranitidine, an antacid, on the absorption of AS-924, a novel prodrug-type cephem antibiotic derived from ceftizoxime (CTIZ), was examined in eight healthy adult male volunteers by the cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. The C(max) and area under the concentration (AUC) values and cumulative urinary excretion rate (0-24 h) of cefteram (CTER) after administration of CTER-PI decreased by 32, 38 and 37%, respectively, in the ranitidine pretreatment group whereas those of AS-924 were not affected by the antacid. The urinary levels of pivaloyl-carnitine determined to evaluate the solubility of these antibiotics in the gastrointestinal tract suggested that this was not affected by ranitidine. These results indicate that the absorption of CTER-PI was affected by pretreatment with ranitidine largely due to inactivation of this antibiotic in the gastrointestinal tract at high pH rather than to a decrease in solubility. In contrast, isomerization of AS-924 was hardly induced by the elevation of pH, thus demonstrating that AS-924 was less likely to be affected by pretreatment with antacids.

Absorption↗

PubMed2001

Effects of the quantity of water and milk ingested concomitantly with AS-924, a novel ester-type cephem antibiotic, on its pharmacokinetics.

The effect of the quantity of water ingested concomitantly with drugs, on the absorption of AS-924, a novel prodrug-type cephem antibiotic, was studied in five healthy adult volunteers by a cross-over method, using cefteram-pivoxil (CTER-PI) as the control drug. In addition, the effect of milk on the absorption of AS-924 was also investigated. The absorption of CTER-PI was significantly reduced when administered together with 30 ml of water compared with its absorption when administered together with 150 ml of water, whereas no such reduction was found in the case of AS-924. Ingestion of milk did not significantly affect the absorption of AS-924. These results confirm that absorption of AS-924 after oral administration is not likely to be affected by the quantity of water taken concomitantly with the drug, nor by milk.

Administration, Oral↗

PubMed2001

Effect of trabecular bone contour on ultimate strength of lumbar vertebra after bilateral ovariectomy in rats.

To test the hypothesis that the effect of trabecular microarchitecture on bone strength varies with the duration of estrogen loss, we evaluated the relationship between three-dimensional (3D) parameters for trabecular microarchitecture and bone minerals with the compressive load of the lumbar vertebra in rats. Female Sprague-Dawley rats (n = 190) were divided into 19 groups. Ten rats were killed at day 0. Half of the remaining rats underwent bilateral ovariectomy (ovx), and the others were subjected to sham surgery. Ten rats from each group were killed at 3, 7, 11, 14, 28, 42, 56, 70, and 84 days postsurgery. Urinary deoxypyridinoline and serum osteocalcin increased significantly in the ovx group from days 28 and 11, respectively, compared with the sham group. Bone mineral content (BMC) and bone mineral density (BMD) of the fifth lumbar body diminished from days 42 and 84, respectively, compared with the sham group. In ovx rats, trabecular bone volume (BV/TV), measured using 3D images of microcomputed tomography, diminished from day 28 compared with both baseline control and sham. The trabecular bone pattern factor (TBPf) and structure model index (SMI) increased from day 28 in the ovx group compared with both baseline control and sham. Ultimate compression loads diminished at day 28 compared with baseline control and decreased progressively thereafter. Neither of these parameters changed in the sham group during the same period. Within 4 weeks post-ovx, TBPf, SMI, and BV/TV correlated with load (p < 0.01). BMC and BMD correlated with load from 6 weeks post-ovx (p < 0.01). Stepwise regression analysis showed that TBPf was the most significant determinant of load within 4 weeks post-ovx (coefficient of determination [R(2)] = 0.669; p < 0.01). SMI correlated with TBPf (R(2) = 0.968; p < 0.01). Moreover, R(2) for ultimate load indicated higher values of 0.975 with TBPf and SMI. However, BMC was the most significant determinant of load from 6 weeks post-ovx (R(2) = 0.511; p < 0.01), as it was in the sham group. These data suggest that changes in trabecular bone contour with increased bone turnover are critical for reducing lumbar bone strength during the early post-ovx period in rats.

Amino Acids↗

PubMed2001

Proteus syndrome.

A case of Proteus syndrome is presented, in which severe hemihypertrophy of the left trunk and left lower extremity, scoliosis, endometriosis and huge bizarre-shaped body tumors were observed. Up to 22.6 kg of tumorous tissue was excised. This syndrome was first described in 1983. The name Proteus comes from a Greek mythical sea god who was able to change his body form freely. This syndrome has numerous features including hemihypertrophy, macrodactyly, various subcutaneous masses, scoliosis and other minor abnormalities. Although diagnostic criteria have been established for Proteus syndrome, which is very difficult to differentiate from other congenital hamartomatous syndromes, more case reports are needed to define such a rare disorder. Our patient is the 6th Japanese case in the English literature.

Adolescent↗

PubMed2001

Phylogenic study of denaturation of lactate dehydrogenase isoenzymes from different species by high and low temperature.

We studied the influence of storage at different temperatures on lactate dehydrogenase (EC 1.1.1.27; LD) isoenzymes from different tissues and different species, and analysed biochemical and biophysical mechanisms of denaturation during storage. Isoenzymes obtained from tissue extracts of mammals, poultry, reptiles. amphibians and fish were shown to have their own denaturation ranges at low temperatures by post-treatment assays and transition temperature analysis. These ranges were between -10 and -20 degrees C for most vertebrate LD isoenzymes. Circular dichroism analysis indicated that the denaturation of LD isoenzymes was probably caused by a change in the hydrophobic interactions in the molecule. At higher temperatures, LD-1 isoenzyme was more thermostable than LD-5 from the same animal species, except for rats, the LD-5 activity of which was more thermostable than the LD-1 activity. These findings indicate that variable effects of storage of samples and reference materials at low temperatures should be considered, and that it is necessary to establish LD isoenzyme standards for animal clinical laboratory investigations.

Animals↗

PubMed2001

Glycolaldehyde-forming route in Bacillus subtilis in relation to vitamin B6 biosynthesis.

Glycolaldehyde (GA) was shown to be a precursor of vitamin B6 (B6), and to be formed from glycolate by glycolaldehyde dehydrogenase (GADH) in Escherichia coli. In this study, we show the glycolaldehyde-forming route in B6 biosynthesis in Bacillus subtilis. In the crude extract of B. subtilis, the oxidizing activity of GADH was detected. However, coexisting NADH/NADPH oxidase activity interfered with the determination of the reducing (GA-forming) activity of GADH. NADH/NADPH oxidase was purified and identified as the product of ahpF. In an ahpF disruptant, NADH/NADPH activity was almost eliminated, but the reducing activity of GADH was not detected. We also investigated another possible GA-forming enzyme, glyoxal reductase (GR). GR was partially purified and identified as the product of yvgN. yvgN disruptant did not require B6, and retained the ability to synthesize the same amount of B6 as the wild-type strain. From these results, we concluded that neither GADH nor GR is involved in B6 biosynthesis in B. subtilis.

Journal Article↗

PubMed2001

[The effects of intravenous nicardipine on jugular venous oxygen saturation].

We investigated the effects of intravenous nicardipine on jugular venous oxygen saturation (SjO2) in patients undergoing superficial temporal artery-middle cerebral artery anastomosis. Anesthesia was induced with intravenous thiamylal and fentanyl, and maintained by isoflurane and nitrous oxide in oxygen. In the presence of stable condition after the induction, nicardipine 0.5 microgram.kg-1.min-1 was administered intravenously for 180 minutes. Mean arterial pressure, heart rate, SjO2 and bladder temperature were recorded. Three hours after continuous infusion of nicardipine, plasma levels of nicardipine in artery and jugular vein were measured by liquid chromatography. The arterial concentration of nicardipine reached 23.9 +/- 8.06 ng.ml-1. The area under the curve between the arterial and jugular venous nicardipine during infusion was significantly different. Mean arterial pressure was reduced in response to administration of nicardipine. There were no significant changes in heart rate, bladder temperature and SjO2. We concluded that the current dose of nicardipine reached effective concentration for systemic hypotension without influencing SjO2.

Adult↗

PubMed2001

[Immunoadsorption therapy for HCV infected chimpanzee].

Response of Interferon therapy to chronic hepatitis C patients are poor who infected high titer of hepatitis C virus(HCV) RNA. It has been reported that HCV particles coexist low density lipoprotein(LDL) or anti-HCV antibodies as antigen-antibody complex in chronic hepatitis C patients. We demonstrated the ability of removal HCV particles by these adsorbents and the efficacy of HCV RNA reduction by immunoadsorption therapy for HCV infected chimpanzee. By batch method, IgG and LDL adsorbent showed 66% HCV RNA reduction and IgG adsorbents kept better adsorption ability than that of others when adsorbent: serum ratio was increased. Immunoadsorption therapy to chronic HCV infected chimpanzee was carried out on-line with a plasma separator. HCV RNA titer of this chimpanzee decreased 35% immediately after therapy, but after 4.5 hours, it recovered as same level as that of before procedure.

Animals↗

PubMed2001

[Blood concentration of propofol during cardiopulmonary bypass--comparison between arterial and internal jugular venous blood].

Twelve adult patients for cardiac surgery were divided into 2 groups, normothermia (6 patients) and mild hypothermia (6 patients), based on their body temperature during cardiopulmonary bypass (CPB). Propofol was continuously administered throughout each operation at a dose of 2 mg.kg-1.h-1. Arterial and internal jugular venous bulb blood samples were drawn simultaneously before CPB, at 5, 30, 60, and 90 minutes after the start of CPB, 30 minutes after the end of CPB, and at the conclusion of the operation, to measure propofol concentrations. In the normothermia group, propofol concentration in the arterial blood decreased significantly 5 minutes after the start of CPB, and then recovered immediately to the pre-CPB value. In the mild hypothermia group, however, no significant change in propofol concentration was observed. In both groups, there was no significant difference in propofol concentration between arterial and internal jugular venous bulb blood throughout the study period. Our results suggest that there are no significant differences between the effect of normothermic and that of mild hypothermic CPB on the pharmacokinetics of propofol in the brain.

Adult↗

PubMed2001

Sodium sulfite and N-acetylcysteine: new additives to dialysate for inhibiting formation of glucose degradation products and advanced glycation end-products.

The present study evaluated the inhibiting effect of various chemicals on the advanced glycation end-product (AGEs) cross-linking caused in protein by glucose degradation products (GDPs). We evaluated a few dozen organic and inorganic chemicals--in addition to previously reported AGE inhibitors, such as thiazolium derivatives and aminoguanidine--for their inhibiting effect. Collagen IV (from human placenta) or human serum albumin (HSA) was incubated with an AGE accelerator and one of the selected chemicals in phosphate buffer solution at 37 degrees C for as long as 14 days. Fluorescence intensity (440 nm) was determined after a given incubation time. Among 36 chemicals tested, 8 new chemicals and 5 previously known AGE inhibitors significantly suppressed the increase in fluorescence intensity seen after incubation of HSA with methylglyoxal. We believe that 6 chemicals may effectively quench GDPs and inhibit AGE cross-link formation, in a manner different from that of aminoguanidine and thiazolium.

Acetylcysteine↗

PubMed2001

[Detection of monoclonal plasma cells in bone marrow and spleen of primary amyloidosis].

A 53-year-old man was diagnosed as primary amyloidosis by biopsy specimens of the mucosa in rectum, spleen and bone marrow (BM). BM examination showed 5.5% of plasma cells with some dysplasia. Immunoglobulin heavy chain gene rearrangement was detected by polymerase chain reaction using third-complementary-determining region (CDR 3) specific primers in BM mononuclear cells and spleen cells embedded in paraffin. The sequence analysis revealed that monoclonal B cells existed in the both, BM and spleen. Flowcytometric analysis using two-color staining showed the phenotype of plasma cells with the expression of CD19+/-, CD27+/-, CD56+/- and CD138+ and CD38++. This phenotype is similar to those of monoclonal gammopathy of undetermined significance (MGUS). Therefore, primary amyloidosis is considered to have two plasma cell populations including normal plasma cells and monoclonal plasma cells in BM. Given that there are two types of plasma cells in patients with primary amyloidosis, amyloid protein is expected to originate from immunoglobulin light chain produced by monoclonal plasma cells.

Amyloid↗