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Biomedical subjects

Y Oda

Publications and source records attributed to Y Oda.

At least 289 records · Page 16Linked to original sources
PubMed1997

Localization and quantification of proliferating cells during rat fracture repair: detection of proliferating cell nuclear antigen by immunohistochemistry.

Bilateral femurs of 12-week-old female Sprague-Dawley rats were fractured, and the fractured femurs were harvested 36 h, 3, 7, 10, and 14 days after the fracture. Localization of cell proliferation in the fracture calluses was investigated using immunohistochemistry with antiproliferating cell nuclear antigen (PCNA) monoclonal antibodies. Thirty-six hours after the fracture, many PCNA-positive cells were observed in the whole callus. The change was not limited to mesenchymal cells at the fracture site where the inflammatory reaction had occurred, but extended in the periosteum along almost the entire femoral diaphysis where intramembranous ossification was initiated. On day 3, periosteal cells or premature osteoblasts in the newly formed trabecular bone during intramembranous ossification still displayed intense staining. On day 7, many premature chondrocytes and proliferating chondrocytes were PCNA positive. Endochondral ossification appeared on days 10 and 14, and the premature osteoblasts and endothelial cells in the endochondral ossification front were stained with anti-PCNA antibodies. Quantification of PCNA-positive cells was carried out using an image analysis computer system, obtaining a PCNA score for each cellular event. The highest score was observed in the periosteum early after the fracture near the fracture site. Immunohistochemistry using anti-PCNA antibodies showed that the distribution of proliferating cells and the degree of cell proliferation varied according to the time lag after the fracture, suggesting the existence of local regulatory factors such as growth factors, and that significant cell proliferation was observed at the beginning of each cellular event.

Animals↗
PubMed1997

Neurotoxicity testing of a new bioactive bone cement.

Bioactive bone cement (BABC) is a novel artificial bone cement. It has some noteworthy characteristics that are applicable to neurological surgery. The toxicity of BABC to the nervous system was tested by implanting BABC and polymethylmethacrylate (PMMA) cement as a control at the parietal and the suboccipital regions of the skull in beagles. The auditory brainstem response (ABR) was tested before and after implantation. Sections of the cerebral cortex and the acoustic nerve were examined at 3 and 6 months after implantation. No abnormal ABR was found in any animals. Histological examination of the cerebral cortex and acoustic nerve demonstrated slight gliosis in both the BABC and PMMA cement groups, but no other abnormalities.

Animals↗
PubMed1997

Mutations in the hepatocyte nuclear factor-1alpha/MODY3 gene in Japanese subjects with early- and late-onset NIDDM.

Recent studies have shown that mutations in the hepatocyte nuclear factor (HNF)-1alpha gene are the cause of maturity-onset diabetes of the young type 3 (MODY3). We have screened 193 unrelated Japanese subjects with NIDDM for mutations in this gene: 83 with early-onset NIDDM (diagnosis at <30 years of age) and 110 with late-onset NIDDM (diagnosis > or = 30 years of age). All of the members of the latter group also had at least one sibling with NIDDM. The 10 exons, flanking introns, and promoter region were amplified using polymerase chain reaction and were sequenced directly. Mutations were found in 7 of the 83 (8%) unrelated subjects with early-onset NIDDM. The mutations were each different and included four missense mutations (L12H, R131Q, K205Q, and R263C) and three frameshift mutations (P379fsdelCT, T392fsdelA, and L584S585fsinsTC). One of the 110 subjects with late-onset NIDDM was heterozygous for the missense mutation G191D. This subject, who was diagnosed with NIDDM at 64 years of age, also had a brother with NIDDM (age at diagnosis, 54 years) who carried the same mutation, suggesting that this mutation contributed to the development of NIDDM in these two siblings. None of these mutations were present in 50 unrelated subjects with normal glucose tolerance (100 normal chromosomes). Mutations in the HNF-1alpha gene occur in Japanese subjects with NIDDM and appear to be an important cause of early-onset NIDDM in this population. In addition, they are present in about 1% of subjects with late-onset NIDDM.

Age Factors↗
PubMed1997

Expression of P-glycoprotein in high grade osteosarcomas with special emphasis on chondroblastic subtype.

The development of chemoresistance is one of the major clinical problems in the therapy of malignant bone tumors in childhood. The expression of membrane-bound P-glycoprotein turned out to be an essential factor in the evidence of resistant tumor cells. To investigate the significance of multidrug resistance in the prognosis of highly malignant osteosarcomas, the immunohistologic expression of P-glycoprotein was investigated in the tumor tissue of 52 patients under special consideration of the histologic subtype. The data were compared with the histologic regression grade in the resection specimen and correlated with clinical data. Formalin-fixed, paraffin-embedded tissue and, additionally, fresh frozen material taken from the primary biopsy were stained using monoclonal antibody JSB1. 29 (55%) of the tumors investigated were P-glycoprotein positive. Considering the response to chemotherapy, no conclusion could be drawn regarding P-glycoprotein expression, regression grade in the resection specimens, and the clinical follow-up. P-glycoprotein was detected in only 52% of the non-responders. A positive reaction was also evidenced in 59% of the patients with high chemosensitivity. A comparison of the histologic subtypes yielded a significant result in the chondroblastic osteosarcomas. 11 of 12 cases showed a strong expression of P-glycoprotein. Most of the cases were non-responders, and using Kaplan-Meier live tables, an unfavorable clinical outcome could be demonstrated. Possibly, chondroblastic tumors have a special position among osteosarcomas because of their differentiation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Effects of 2'-substituents of the first deoxyguanosine residue in the recognition sequence of EcoRI restriction endonuclease activity.

The effects of 2'-substituents of the first deoxyguanosine on EcoRI activity were examined using synthetic octadeoxynucleotides D(GG*AATTCC) containing 2'-substituted derivatives (G*), i.e., 2'-fluoro-2'-deoxyguanosine (dGfl), 2'-chloro-2'-deoxyguanosine (dGcl), and guanosine (rG). The overall structures of the octamers were very similar, as shown by CD and UV measurements, although their EcoRI reactivities were very different: 100% in 60 min for d(GGAATTCC) and d(GGflAATTCC), 5% in 24 h for d[G(rG)AATTCC], and no cleavage at all in 24 h for d(GGclAATTCC). However, the kinetics showed the octamers exhibit similar binding-affinity to the enzyme (10(-6)-10(-7) M). 31P-NMR analysis suggested the modified octamers change the phosphate backbone conformation in a duplex, since an unusual downfield-shifted signal in the spectra was commonly observed for the modified octamers at low temperature (i.e., a duplex state), which was shifted upfield at high temperature (i.e., a single strand state). The order of the differences was dGcl > rG > dGfl-containing octamers, coinciding with that of the vdW volume of 2'-substituents (Cl > OH > F) and the cleavage reactivities. These findings suggest that steric hindrance by the 2'-substituents causes of conformational change of the phosphate backbone close to the scissile bond, and then interferes with the EcoRI reaction.

Binding Sites↗
PubMed1997

[Two cases of crush syndrome associated with intractable pain].

We describe two patients (a 21-year-old woman and a 26-year-old man) with crush syndrome who were injured by being buried under collapsed buildings in the Kobe-Awaji Earthquake, and thereafter developed severe pain in the affected limbs. On arrival at our ICU 3 days after the injury, sensation and muscular power were completely absent in both patients. Emergent fasciotomy was performed for the woman. In both patients, burning pain and allodynia occurred in the affected legs between 1 and 3 weeks following the injury while sensation and muscular power partially recovered over the same time period. Pain was not effectively controlled by oral or intramuscular analgesics. Continuous epidural analgesia with 0.25% bupivacaine at a rate of 2 ml.h-1 was effective for relieving pain in the woman, but was not effective in the man, for whom supplemental analgesics, transcutaneous nerve stimulation and near infrared radiation were required to relieve pain. We conclude that persistent pain is one of the important complications of crush syndrome, and that early treatment of pain including epidural analgesia is necessary and may improve functional prognosis of affected patients.

Adult↗
PubMed1997

Effect of phenobarbital on the pharmacokinetics of lidocaine, monoethylglycinexylidide and 3-hydroxylidocaine in the rat: correlation with P450 isoform levels.

To elucidate the effect of cytochrome P450 levels in hepatic microsomes on the metabolism of lidocaine in vivo, we investigated the metabolism of lidocaine in untreated (UT group) and phenobarbital-treated rats (PB group) in vivo and compared the results with those obtained by immunoblotting of rat hepatic microsomes. There were no differences in pharmacokinetic parameters for lidocaine between the UT and PB groups. The plasma concentrations of the N-deethylated metabolite of lidocaine, monoethyl-glycinexylidide (MEGX), in the PB group were significantly higher than those in the UT group. On the other hand, the plasma concentrations of the aromatic ring hydroxylated metabolite of lidocaine, 3-hydroxylidocaine (3-OH LID), were significantly lower in the PB group than in the UT group. When lidocaine metabolism was studied with hepatic microsomes prepared from rats in the UT and PB groups, the rates of formation of MEGX were higher in the microsomes of the PB group than in those of the UT group. The contents of CYP2B1 and 3A2 in rat hepatic microsomes of the BP group measured by immunoblotting were significantly higher than those of the UT group. Strong correlations were found between the area under the plasma concentration vs. time curve for MEGX and specific contents of CYP2B1 and 3A2. These findings suggest that formation of MEGX in vivo is dependent on the levels of CYP2B1 or 3A2 in rat liver.

Anesthetics, Local↗
PubMed1997

Soldering strength of post-soldering of palladium-based metal-ceramic alloys.

To evaluate the post soldering of metal-ceramic alloys that have palladium as their main component, palladium-based metal-ceramic alloys with different compositions were used to assess soldering strength. Four palladium-based metal ceramic alloys were selected: Pd-Cu system, Pd-Ag system, Pd-Ni system, and Pd-Sb system, and gold-silver-palladium alloy was also used. As soldering materials, 12 k gold solder and 16 k gold solder were used. After post-soldering by butt joint samples that had been heat treated (equivalent to the porcelain firing cycle), soldering strength was evaluated by measuring the flexural strength. The yield strength had a range of 300 to 800 MPa, and the ultimate strength was in the range of 350 to 1,000 MPa; the Pd-Ag type showed the highest value. There was no correlation between the yield strength of the metal-ceramic alloys and that of the soldering samples. When the soldering strength of 12 k gold solder and 16 k solder were compared, the samples soldered with 12 k gold solder showed higher values in all cases. Samples in which heating was prolonged for 10 seconds had a high strength, within 100 to 500 MPa in yield strength and 100 to 800 MPa in ultimate strength.

Analysis of Variance↗
PubMed1997

Corrosion resistance of the soldering joint of post-soldering of palladium-based metal-ceramic alloys.

To evaluate the corrosion resistance of post soldering of metal-ceramic alloys, four commercially available palladium-system metal-ceramic alloys (Pd-Cu, Pd-Ni, Pd-Ag, and Pd-Sb systems) and two types of solder (12 k gold solder and 16 k gold solder) with different compositions and melting points were used. The corrosion resistance of the soldered joint was evaluated by anodic polarization. The electrochemical characteristics of soldered surface were measured using electrochemical equipment. Declines in corrosion resistance were not detectable with Pd-Cu, Pd-Ag and Pd-Sb types, but break down at low potential occurred with Pd-Ni type.

Corrosion↗
PubMed1997

A study on the grinding accuracy of a copy milling machine for dental use.

In order to assess the relationship between the profiling pressure of a copy milling machine for dental use and the accuracy of the dimensions of the objects produced, a Celay System was used to profile a metal-cylinder model, and its dimensions were compared with the workpieces. The results showed that, when a cylindrical model with a diameter of 6 mm was subjected to freehand profiling, the mean processing error of the object produced was -0.026 mm, and the profiling pressure was 4.6 gf to 131.7 gf (mean: 76.6 gf). However, the fluctuations in profiling pressure decreased by 1/5 during profiling operations when accessories that fixed the profiling pressure and the profiling loci were used. Moreover, while the processing error when the model was profiled at a profiling pressure of 76 gf or less was a mere 0.005 mm, at 110 gf it rose to 0.022 mm. Based on the above, the processing error that occurred as a result of profiling pressure appeared to affect processing accuracy. On the basis of these findings, profiling as light weight must be performed with as possible in order to obtain accurate products using the copy milling machine for dental use, and the results suggested the necessity of attaching control devices to the copy milling machine to make accurate restorations.

Calibration↗
PubMed1996

Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)

The disease non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is characterized by abnormally high blood glucose resulting from a relative deficiency of insulin. It affects about 2% of the world's population and treatment of diabetes and its complications are an increasing health-care burden. Genetic factors are important in the aetiology of NIDDM, and linkage studies are starting to localize some of the genes that influence the development of this disorder. Maturity-onset diabetes of the young (MODY), a single-gene disorder responsible for 2-5% of NIDDM, is characterized by autosomal dominant inheritance and an age of onset of 25 years or younger. MODY genes have been localized to chromosomes 7, 12 and 20 (refs 5, 7, 8) and clinical studies indicate that mutations in these genes are associated with abnormal patterns of glucose-stimulated insulin secretion. The gene on chromosome 7 (MODY2) encodes the glycolytic enzyme glucokinases which plays a key role in generating the metabolic signal for insulin secretion and in integrating hepatic glucose uptake. Here we show that subjects with the MODY3-form of NIDDM have mutations in the gene encoding hepatocyte nuclear factor-1alpha (HNF-1alpha, which is encoded by the gene TCF1). HNF-1alpha is a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene.

Animals↗
PubMed1996

Crystallization and preliminary X-ray diffraction analysis of two lysinal derivatives of Achromobacter protease I.

Two crystal forms of lysinal derivatives of Achromobacter protease I have been obtained. The first, modified by benzyloxycarbonyl-Val-lysinal crystallizes in the monoclinic space group P2(1) with unit-cell dimensions of a = 39.6, b = 71.2, c = 45.6 A and beta = 98.4 degrees. The second, modified by benzyloxycarbonyl-Leu-Leu-lysinal crystallizes in the orthorhombic space group I222 (or I2(1)2(1)2(1)) with unit-cell dimensions of a = 98.7, b = 102.2 and c = 55.8 A. The space groups and the unit-cell dimensions of the present two lysinal derivatives are different to those of the protease and TLCK- modified one. The space group of the protease is P1 with cell dimensions a = 39.53, b = 40.34, c = 43.92 A, alpha = 114.81, beta = 113.75 and gamma = 74.00 degrees and that of the TLCK-modified one is also P1 with cell dimensions of a = 37.30, b = 42.74, c = 48.02 A, alpha = 120.10, beta = 112.81 and gamma = 68.54 degrees. Diffraction to 1.9 A resolution for the Val-lysinal modified crystal and to 2.2 A resolution for the Leu-Leu-lysinal modified crystal has been observed using a rotating-anode X-ray generator. Full structure determinations of these lysinal-modified protease crystals may lead to an understanding of the molecular basis of enzyme-substrate interactions in the catalytic process of this protease.

Journal Article↗
PubMed1996

Hydroxylforms of p-boronophenylalanine as potential boron carriers on boron neutron capture therapy for malignant brain tumors.

Hydroxylforms of boronophenylalanine (BPA) were synthesized by conjugation with a cascade of polyols to decrease the BPA uptake of normal parenchyma without affecting uptake into the tumor. We determined their tumor cell killing effect on boron neutron capture therapy (BNCT) against BPA using the human glioma cell line T98G. The thermal neutron doses yielding the D37 (dose used to inhibit 63% colony formation) values of dl-p-BPA(OH)n were 1.45 x 10(12)nvt (n = 1), 1.33 x 10(12)nvt (n = 2), 3.37 x 10(12)nvt (n = 4), and 1.72 x 10(12)nvt (n = 0). The relative tumor cell killing effect on BNCT of dl-p-BPA(OH)n against dl-p-BPA, which was defined as the ratio of D37-BPA to D37-BPA(OH)n, was 1.18 (n = 1) 1.29 (n = 2), and 0.51 (n = 4). The tumor:normal brain ratio of dl-p-BPA(OH)n in 9L rat brain tumor models was improved 1.2- (n = 1) and 1.4-fold (n = 2) against that of dl-p-BPA without a decrease of its uptake into the tumor. The water solubility of BPA(OH)n increased against BPA, and the toxicity represented as the IC50 value of dl-p-BPA(OH)2 was nearly one half that of dl-p-BPA, being established in our previous works. Hydroxylforms of BPA, especially dl-p-BPA(OH)2, might be more suitable boron carriers of BNCT to malignant brain tumors since the radiation injury to the normal parenchyma surrounding the tumor is reduced.

Animals↗
PubMed1996

7-Ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in human liver microsomes.

7-Ethoxycoumarin O-deethylation has been used widely as a marker activity for assessing substrate specificities of cytochromes P450 (P450) in liver microsomes of mammals, and extensive studies have shown that in rats and mice the major catalysts are P450 1A1, 1A2, and 2B enzymes. In contrast to findings in experimental animal models, P450 2E1 has been reported to be a principal enzyme involved in 7-ethoxy-coumarin O-deethylation in human livers. In this study, we further examined the roles of individual forms of human P450 involved in 7-ethoxycoumarin O-deethylation using microsomes from different human liver samples and from human lymphoblastoid cells expressing human P450 enzymes and purified P450 enzymes isolated from the membrane of Escherichia coli expressing modified P450 proteins. Kinetic analysis showed that there were at least two different enzymes involved in 7-ethoxycoumarin O-deethylation in different human samples. Samples that contained high amounts of P450 2E1 in liver microsomes showed biphasic curves for O-deethylation with relatively high turnover numbers, whereas P450 1A2-rich samples tended to have low Km values with low Vmax values. Anti-human P450 2E1 antibodies inhibited markedly (P < 0.05) the 7-ethoxycoumarin O-deethylation activities catalyzed by human liver microsomes particularly when examined at a high substrate concentration (200 microM). However, we also found that anti-P450 1A2 antibodies suppressed O-deethylation activities only at a low substrate concentration (10 microM). Recombinant human P450 1A2 was found to have a low Km value for 7-ethoxycoumarin O-deethylation, whereas P450 2E1 showed a high Km value. Of the P450 enzymes examined, P450 1A1 gave the highest O-deethylation activities with a low Km value, although this enzyme is reported to be expressed extrahepatically in humans. Other human P450 enzymes, including P450 2A6, 2C10, 2D6, 3A4, and 3A5, did not show significant O-deethylation activities except that P450 2B6, a minor P450 component in human livers, was found to have a Vmax value similar to that of P450 1A2 and a Km value similar to that of P450 2E1. These results suggest that P450 1A2 is a low Km enzyme for 7-ethoxycoumarin O-deethylation in human liver microsome, although it has a low Vmax value than P450 2E1.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1996

Expression of multidrug-resistance-associated protein gene in human soft-tissue sarcomas.

We examined the mRNA expression of the multidrug- resistance-associated protein gene (MRP) in soft-tissue sarcomas and compared it with the expression of the multidrug resistance gene (MDR1), using the reverse transcriptase/polymerase chain reaction. We investigate 39 samples from 33 cases of soft-tissue sarcomas (11 liposarcomas, 9 malignant fibrous histiocytomas, 6 leiomyosarcomas, 4 malignant schwannomas, 3 fibrosarcomas, 3 synovial sarcomas, and 3 epithelioid sarcomas) and 7 benign soft-tissue tumors. All samples were obtained prior to chemotherapy. An expression of MRP mRNA was noted in 56% of soft-tissue sarcoma specimens. The co-expression of MRP and MDR1 was recognized in 15 samples (38%) (5/11 liposarcomas, 5/9 malignant fibrous histiocytomas, 3/6 leiomyosarcomas, 2/3 fibrosarcomas) and significantly correlated with histological grade (P=0.0165). A positive and significant correlation was found between MRP and MDR1 expression in soft-tissue sarcomas(P=0.0013). In benign soft-tissue tumors, 1 chemodectoma and 1 neurothekeoma showed low MRP expression; however, no case showed co-expression of MRP and MDR1.

ATP-Binding Cassette Transporters↗
PubMed1996

Localization of choline acetyltransferase and acetylcholine in the chorion of early human pregnancy.

This report concerns the activity of choline acetyltransferase (ChAT), and the localization of ChAT and acetylcholine (ACh) in the human chorion during the 5th to 10th weeks of gestation. Radio-enzyme, immunohistochemical, and in situ hybridization assays were used. We found that ChAT activity increases as a function of gestational age between the 5th and the 9th weeks of pregnancy. At 5 weeks' gestation, ChAT was detected by immunohistochemical means mainly in cytotrophoblast and villous stromal cells, particularly in the cytotrophoblastic shell and cell columns. With the development of blood vessels at the 6th week, their endothelial cells also expressed ChAT. The amount of ChAT immunoreaction product deposits decreased in the villous cytotrophoblast by the 9th and 10th weeks when the layer of the cell became flat. By comparison, ChAT protein was detected only rarely in the syncytiotrophoblast layer during the gestation period studied. The ChAT gene transcript was demonstrated in most of the constitutive cells of the chorion. However, in contrast to the results of the immunohistochemical assays, positive hybridization signals for ChAT mRNA were evenly distributed over both cytotrophoblast and syncytiotrophoblast. On the other hand, the distribution of ACh immunoreaction products was almost coincident with that of ChAT.

Acetylcholine↗