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Biomedical subjects

T Taguchi

Publications and source records attributed to T Taguchi.

At least 55 records · Page 3Linked to original sources

Collagen-binding heat shock protein HSP47 expression during healing of fetal skin wounds.

Wounds in fetal animals are known to heal without scar formation, but the mechanism involved remains unclear. Scar tissue is characterized by disorganized collagen bundles. The 47-kDa heat shock protein (HSP47) is a molecular chaperone that specifically targets collagen processing. However, the role of HSP47 in scar formation is poorly understood. We studied the relation of HSP47 expression in skin to scar formation during fetal wound healing. Immunohistochemical analysis demonstrated HSP47-positive cells in the epidermal cell layer of fetal and neonatal rat skin and the absence of such cells in subcutaneous tissue. After induction of a wound on the back of fetal and neonatal rats, the message of collagen type I was increased only in neonatal skin but not in fetal skin. HSP47-positive cells consistently increased for 7 days after wound induction in neonatal rats. In contrast, HSP47-positive cells and HSP47 protein were unchanged in fetal rats. We conclude that the scarless healing of fetal skin wounds is related to lack of change in HSP47 expression. HSP47 may thus be an important determinant of scar formation during wound healing.

Animals↗

Aminoguanidine pyridoxal adduct is superior to aminoguanidine for preventing diabetic nephropathy in mice.

Aminoguanidine inhibits the formation of advanced glycation end-products, and has been extensively examined in animals. However, administration of aminoguanidine decreases the hepatic content of pyridoxal phosphate. In order to avoid this problem, we developed an aminoguanidine pyridoxal Schiff base adduct and examined its efficacy in vitro as well as in a model of diabetic nephropathy. Mice with streptozotocin-induced diabetes were treated with aminoguanidine or aminoguanidine pyridoxal adduct for 9 weeks. An in vitro study was also performed to assess the antioxidant activity of aminoguanidine and its pyridoxal adduct. Neither drug altered glycemic control. Aminoguanidine pyridoxal adduct significantly improved urinary albumin excretion by 78.1 % compared with the diabetic control, and also had a better preventive effect on the progression of renal pathology than aminoguanidine did. Inhibition of glycation by both drugs was similar, but the antioxidant activity of the pyridoxal adduct was far superior. These findings suggest that aminoguanidine pyridoxal adduct may be superior to aminoguanidine, as it not only prevents vitamin B6 deficiency but is also better at controlling diabetic nephropathy, as this adduct inhibits oxidation as well as glycation.

Animals↗

Efficient selection of genomic clones from a female chicken bacterial artificial chromosome library by four-dimensional polymerase chain reactions.

A bacterial artificial chromosome (BAC) library consisting of 49,152 genomic clones was constructed from partially HindIII-digested female chicken embryo genomic DNA using the pBAC-Lac vector and maintained in 512 96-well plates. The mean insert size was approximately 150 kb, and the total library was estimated to contain about 3.2 times coverage of the diploid genome. In order to screen this library by the PCR, 296 BAC clone DNA samples were prepared: one sample each from 8 superpools (64 plates per superpool) and 36 samples of four-dimensionally (4-D) mixed clones from each superpool. A BAC clone of interest was selected by two-step PCR. First, 8 DNA samples representing superpools were subjected to PCR with a set of primers to amplify a part of the genomic sequence of interest. Second, 36 4-D DNA samples from the superpool that contained BAC clone(s) of interest were subjected to PCR with the same set of primers. The second step identified a plate and a well containing the BAC clone of interest. Selection of target BAC clone(s) from the whole library with the above procedure can be achieved within 1 to 4 d without using a radioactive probe. This procedure was applied successfully in the selection of BAC clones for Wpkci, chPKCI/HINT, ZOV3, and 17beta-HSD genes.

Amino Acid Sequence↗

Swelling behavior of hyaluronic acid and type II collagen hydrogels prepared by using conventional crosslinking and subsequent additional polymer interactions.

Polymer-polymer interactions, such as hydrophobic and electrostatic interactions, were introduced into covalently crosslinked composite matrices consisting of an anionic polysaccharide, hyaluronic acid (HyA) and a cationic polypeptide, type II collagen. The matrices were covalently crosslinked using a water soluble carbodiimide (WSC; 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride) and were immersed at different temperatures in excess water or 0.4 M NaCl aqueous solution, i.e. the optimal salt concentration to suppress polyion complex formation. Hydrophobic interaction was introduced in the matrices when the temperature was increased. Matrices with polymer-polymer interactions could be obtained when immersed in water at 37 degrees C without any collagen denaturation. The molar ratios of [OH]/[COOH] and [NH2]/[COOH], and WSC concentration in precursor solutions of HyA-collagen composite matrices influenced the electrostatic interactions. The hydrophobic and electrostatic interactions in the matrix were maintained in water, even at low temperatures, while in salt solutions at elevated temperatures, these interactions were nullified.

Biocompatible Materials↗

Glomerulocystic kidney disease (GCKD) associated with Henoch-Schoenlein purpura: a case report and a review of adult cases of GCKD.

We report on a 71-year-old male with Henoch-Schoenlein purpura (HSP) who developed glomerulocystic kidney disease (GCKD) without congenital abnormality. He had mild renal dysfunction. Renal biopsy findings showed mild proliferation of mesangial cells and matrixes, and tubular atrophy, interstitial fibrosis, cystic dilation of Bowman's capsule and atrophy of the glomerular tuft. The deposition of IgA and C3 in the mesangial area was observed with the fluorescent antibody technique. Therefore he was diagnosed with GCKD-associated HSP. This was the oldest patient among the previous case reports and the patient was the first case to be reported for concurrent GCKD and HSP. In this study, we also reviewed the patient to previously reported adult patients with GCKD.

Aged↗

Reassessment of the diagnostic value of selective lumbosacral radiculography.

In nerve root infiltration (NRI) consisting of neural blockage and radiculography, response to the nerve root block has usually been thought to be diagnostically significant. However radiculography has not been statistically evaluated. The purpose of this paper is to assess the value of selective radiculography of patients with group 1 response (typical pain reproduced by needle placement and then relieved by nerve root block) according to Dooley's criteria. We studied selective radiculography in a consecutive series of 88 patients with lumbo-sacral radicular pain who showed group 1 response in NRI. The accuracy of the preoperative nerve root block and radiculography in 88 nerve roots (L5,S1) were correlated with the intraoperative findings. Selective radiculograms were classified into three groups; normal (absence of block), partial block, and complete block. The tilting angle of all nerve roots was measured. We found the symptomatic root at the same level of the nerve root block in all 88 patients. Selective radiculograms showed five normal roots, 15 roots with incomplete block and 63 roots with complete block. Fifteen radiculograms had abnormal tilting angles. The accuracy of radiculography was 84% in the canal zone and 100% in the intra and extraforaminal zones. If the L5 nerve root angle was more than 60(o), an intra or extraforaminal lesion was strongly suggested (P<0.01). Radiculography of patients with group 1 response is useful for detecting compressed sites in the symptomatic nerve root, particularly for detecting lesions in the intra and extraforaminal zones.

Adult↗

Analysis of the infection system of human T-cell leukaemia virus type I based on a mathematical epidemic model.

Human T-cell leukaemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). HTLV-I has existed in Japanese people for thousands of years. In order to prevent an epidemic of HTLV-I, it is important to explain the infection system by a mathematical approach. By considering the main infection routes in Japan, that is: (i) mother-to-child transmission; (ii) male (husband)-to-female (wife) transmission; and (iii) female (wife)-to-male (husband) transmission, a mathematical model for describing the time-dependent change of the infection proportion can be constructed. An upper bound of the present infection rate per year in male-to-female transmission and that in female-to-male transmission is given by the model, and theoretical results related to HTLV-I infection are also deduced from the mathematical model. A simulation study based on the present model demonstrates the theoretical results relating to the HTLV-I infection.

Computer Simulation↗

Involvement of up-regulation of 17beta-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers.

Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 +/- 17.5 pg/g) (mean +/- SE) were not significantly different from those of premenopausal patients (110.1 +/- 10.1 pg/g) (p = 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17beta-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17beta-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients.

17-Hydroxysteroid Dehydrogenases↗

A new mode of stereochemical control revealed by analysis of the biosynthesis of dihydrogranaticin in Streptomyces violaceoruber Tü22.

A class of Streptomyces aromatic polyketide antibiotics, the benzoisochromanequinones, all shows trans stereochemistry at C-3 and C-15 in the pyran ring. The opposite stereochemical control found in actinorhodin (3S, 15R, ACT) from S. coelicolor A3(2) and dihydrogranaticin (3R, 15S, DHGRA) from S. violaceoruber Tü22 was studied by functional expression of the potentially relevant ketoreductase genes, actIII, actVI-ORF1, gra-ORF5, and gra-ORF6. A common bicyclic intermediate was postulated to undergo stereospecific reduction to provide either the 3-(S) or the 3-(R) configuration of an advanced intermediate, 4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho[2,3-c]pyran-3-acetic acid (DNPA). Combinations of the four ketoreductase genes were coexpressed with the early biosynthetic genes encoding a type II minimal polyketide synthase, aromatase, and cyclase. gra-ORF6 was essential to produce (R)-DNPA in DHGRA biosynthesis. Out of the various recombinants carrying the relevant ketoreductases, the set of gra-ORF5 and -ORF6 under translational coupling (on pIK191) led to the most efficient production of (R)-DNPA as a single product, implying a possible unique cooperative function whereby gra-ORF6 might encode a "guiding" protein to control the regio- and stereochemical course of reduction at C-3 catalyzed by the gra-ORF5 protein. Updated BLAST-based database analysis suggested that the gra-ORF6 product, a putative short-chain dehydrogenase, has virtually no sequence homology with the actVI-ORF1 protein, which was previously shown to determine the 3-(S) configuration of DNPA in ACT biosynthesis. This demonstrates an example of opposite stereochemical control in antibiotic biosynthesis, providing a key branch point to afford diverse chiral metabolic pools.

Alcohol Oxidoreductases↗

Accumulation of oxidative DNA damage, 8-oxo-2'-deoxyguanosine, and change of repair systems during in vitro cellular aging of cultured human skin fibroblasts.

Effects of in vitro cellular aging on the content of 8-oxo-2'-deoxyguanosine, a typical oxidation product of DNA bases, were examined in cultured human skin fibroblasts. The 8-oxo-2'-deoxyguanosine content in the DNA of TIG-3S cells established from skin tissues of a fetal donor increased immediately before the cessation of proliferation. TIG-114 and TIG-104 cells established from skin tissues of adult and aged donors, respectively, showed similar changes in 8-oxo-2'-deoxyguanosine content during in vitro cellular aging. The accumulation of 8-oxo-2'-deoxyguanosine in late-passage cells was dependent on the number of cell divisions, and not on the cultivation time. Increases in the activities of superoxide dismutase and glutathione peroxidase were observed prior to the increase in 8-oxo-2'-deoxyguanosine content, while the catalase activity decreased gradually during in vitro cellular aging at late-passage. Furthermore, the activities of 8-oxo-2'-deoxyguanosine endonuclease and DNA polymerases decreased with the progression of proliferation. These results indicate that defense systems against oxidative stress in late-passage cells remain sufficiently active before the cessation of cell division, but that repair systems against oxidative damage decay at late-passage. Oxidative stress beyond the antioxidant capacity and/or repair activity seems to result in an accumulation of 8-oxo-2'-deoxyguanosine in late-passage cells.

8-Hydroxy-2'-Deoxyguanosine↗

PKC and CaMKII dependent synaptic potentiation in cultured cerebral neurons.

We have reported that the long-lasting potentiation of spontaneous excitatory postsynaptic currents (SEPSCs) was induced by a Mg(2+)-free treatment in cultured chick cerebral neurons and a factor(s) extracellularly released during the treatment could induce the potentiation by itself. In this paper, protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase type II (CaMKII) but not protein kinase A (PKA) were reported to contribute to the potentiation mechanism during a step between the activation of the N-methyl-D-aspartate receptors by the Mg(2+)-free treatment and the secretion of the protein factor(s).

8-Bromo Cyclic Adenosine Monophosphate↗

Kinetic analysis of binding between Shiga toxin and receptor glycolipid Gb3Cer by surface plasmon resonance.

Shiga toxin (Stx) binds to the receptor glycolipid Gb3Cer on the cell surface and is responsible for hemolytic uremic syndrome. Stx has two isoforms, Stx1 and Stx2, and in clinical settings Stx2 is known to cause more severe symptoms, although the differences between the mechanisms of action of Stx1 and Stx2 are as yet unknown. In this study, the binding modes of these two isoforms to the receptor were investigated with a surface plasmon resonance analyzer to compare differences by real time receptor binding analysis. A sensor chip having a lipophilically modified dextran matrix or quasicrystalline hydrophobic layer was used to immobilize an amphipathic lipid layer that mimics the plasma membrane surface. Dose responsiveness was observed with both isoforms when either the toxin concentration or the Gb3Cer concentration was increased. In addition, this assay was shown to be specific, because neither Stx1 nor Stx2 bound to GM3, but both bound weakly to Gb4Cer. It was also shown that a number of fitting models can be used to analyze the sensorgrams obtained with different concentrations of the toxins, and the "bivalent analyte" model was found to best fit the interaction between Stxs and Gb3Cer. This shows that the interaction between Stxs and Gb3Cer in the lipid bilayer has a multivalent effect. The presence of cholesterol in the lipid bilayer significantly enhanced the binding of Stxs to Gb3Cer, although kinetics were unaffected. The association and dissociation rate constants of Stx1 were larger than those of Stx2: Stx2 binds to the receptor more slowly than Stx1 but, once bound, is difficult to dissociate. The data described herein clearly demonstrate differences between the binding properties of Stx1 and Stx2 and may facilitate understanding of the differences in clinical manifestations caused by these toxins.

Bacterial Toxins↗

Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer.

The clinical usefulness of BRCA1 and BRCA2 mRNA levels in tumor tissues in the prediction of response to docetaxel (DOC) treatment has been studied in breast-cancer patients. Twenty-five patients with locally advanced breast tumors (n = 13) or locally recurrent tumors (n = 12) underwent tumor biopsy and were treated with DOC (60 mg/m2 every 3 weeks). BRCA1 and BRCA2 mRNA levels in the tumors were determined by real-time PCR, and the expression of 6 biological markers (P-glycoprotein, p53, erbB2, BCL2, MIB1, estrogen receptor-alpha) in the tumors was determined by immunohistochemistry. BRCA2 mRNA levels (0.547 +/- 0.200, mean +/- SE) of responders to DOC treatment were significantly (p < 0.05) lower than those of non-responders (1.538 +/- 0.358), but there was no significant difference in BRCA1 mRNA levels between responders (0.389 +/- 0.081) and non-responders (0.779 +/- 0.172). Tumors were dichotomized into groups with high or low BRCA2 mRNA levels according to the cut-off value of 0.13. The response rate (25%) of tumors with high BRCA2 mRNA levels was significantly (p < 0.01) lower than that (100%) of tumors with low BRCA2 mRNA levels. Positive predictive value, negative predictive value and diagnostic accuracy of the BRCA2 mRNA assay in the prediction of response to DOC were 100%, 75% and 80%, respectively. No significant difference was found between responders and non-responders in the expression status of any of the other 6 biological markers. These results suggest that BRCA2 mRNA levels in tumor tissues might be clinically useful in the prediction of response to DOC treatment in breast-cancer patients.

Adult↗

Prediction of chemotherapeutic response by Technetium 99m--MIBI scintigraphy in breast carcinoma patients.

BACKGROUND: Significance of Technetium 99m ((99m)Tc)-MIBI scintigraphy in the prediction of response to anthracylines and taxanes (both are substrates for P-glycoprotein [P-gp]) as well as relation between (99m)Tc-MIBI uptake and P-gp or MDR1 mRNA expression in tumors were studied in patients with breast carcinoma. METHODS: Forty-six female patients with locally advanced (n = 15) or metastatic (n = 31) breast carcinoma were recruited in this study. Before chemotherapy (epirubicin and cyclophosphamide [n = 20] or decetaxel [n = 26]), (99m)Tc-MIBI scintigraphy was performed to obtain the T/N (tumor to normal tissue) ratios of (99m)Tc-MIBI uptake at 10 minutes (T/N[e]) and at 180 minutes (T/N[d]) after the (99m)Tc-MIBI injection. Expression of MDR1 mRNA and P-gp in tumors (n = 32) were determined by a quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Clinical significance of T/N(e) and T/N(d) ratios in the prediction of chemotherapeutic response was evaluated using the arbitrary cutoff values of 3.0 for T/N(e) ratios and 2.0 for T/N(d) ratios. Positive predictive value, negative predictive value, and diagnostic accuracy of T/N(d) ratios (81.0%, 96.0%, and 89.1%, respectively) were higher, although statistically not significant, than those of T/N(e) ratios (73.3%, 77.4%, and 76.1%, respectively), and these values were not affected by type of chemotherapy. MDR1 mRNA levels were not significantly different between the lesions with high (> or = 2.0) and low (< 2.0) T/N(d) ratios, but P-gp expression was significantly (P < 0.01) higher in the lesions with low T/N(d) ratios than in those with high T/N(d) ratios. CONCLUSIONS: T/N(d) ratios determined by (99m)Tc-MIBI scintigraphy are useful in the prediction of response to chemotherapy with epirubicin and cyclophosphamide or docetaxel as well as in the in vivo evaluation of P-gp expression status in tumors in patients with locally advanced or recurrent breast carcinoma.

ATP Binding Cassette Transporter, Subfamily B↗

A correlation between magnetic resonance imaging and electrophysiological findings in cervical spondylotic myelopathy.

STUDY DESIGN: Correlation between compressed spinal cords on magnetic resonance imaging (MRI) and electrophysiological findings in cervical spondylotic myelopathy patients. OBJECTIVE: To clarify the correlation between spinal-cord-evoked potentials and MRI measurements of compressed spinal cords in patients with cervical spondylotic myelopathy. SUMMARY OF BACKGROUND DATA: Compression of the spinal cord does not always cause clinical symptoms and it is difficult to infer the degree of dysfunction of the spinal cord from MRI findings. METHODS: Seventeen patients with cervical spondylotic myelopathy were examined with MRI and spinal-cord-evoked potentials before surgery. Using abnormality in spinal-cord-evoked potentials as indicators of spinal cord morphology, spinal-cord transverse area and compression ratios (central and 1/4-lateral) were measured on T1-weighted axial imaging. The correlations between these dimensions and electrophysiological findings were investigated. RESULTS: The mean preoperative transverse area of the spinal cord was 47.13 mm2. The mean preoperative central compression ratio of the spinal cord was 34.4%. The mean preoperative 1/4-lateral compression ratio of the spinal cord was 27.5%. A correlation (Spearman r=0.65, P < 0.01) was observed between the 1/4-lateral compression ratio of the spinal cord and the amplitude ratio of spinal-cord-evoked potentials after electric stimulation of the brain (Br(E)-SCEPs). CONCLUSIONS: The preoperative 1/4-lateral compression ratio of the spinal cord was found to reflect the degree of dysfunction of the corticospinal tracts.

Adult↗

Differential recording of upper and lower cervical N13 responses and their contribution to scalp recorded responses in median nerve somatosensory evoked potentials.

To distinguish the different origins of cervical N13 potentials in median nerve somatosensory evoked potentials (SSEPs), cervical N13 potentials were recorded by two different montages. The abnormal patterns of the SSEPs were compared to the abnormal evoked spinal cord responses (ESCPs) recorded from posterior epidural space in 13 patients with various cervical lesions. SSEPs from the posterior cervical surface were recorded from the mid-cervical level with anterior neck reference (Cv5-AN) and from the upper cervical level with inion reference (Cv2-IN). Scalp responses were recorded from the parietal region contralateral to the stimulating side with non-cephalic reference (shoulder contralateral to stimulating side). ESCPs were recorded from the posterior epidural space using catheter electrodes or needle electrodes inserted into the ligamentum flavum. Lower cervical N13 (LC-N13) recorded from the Cv5-AN montage showed similar latency to upper cervical N13 (UC-N13) recorded from the Cv2-IN montage. The latency of the early part of the P13-P14 complex in the scalp montage was similar to that of the UC-N13 and the negative peak latency of the ESCPs recorded at the C2-3 level. Attenuation of the LC-N13 and relatively preserved UC-N13 and P13-P14 were characteristic in patients with cervical syringomyelia and compression cervical myelopathy at the mid-cervical levels. Attenuation of the UC-N13 with normal LC-N13 was characteristic in patients with cervical spondylotic myelopathy who showed conduction blockade of the ESCPs at the C3-4 level. In a patient with schwannoma at the C1-2 level, conduction blockade of the ESCPs was observed at the C1-2 level. P13 was normal but P14 was prolonged. UC-N13 and P13 latencies were similar to the negative peak latency of the ESCPs at the C2-3 level. We demonstrated that two different cervical N13 potentials can be recorded by two different montages and they represent different behavior in various spinal cord lesions. In addition, at least the early part of the P13-P14 complex originates in the upper cervical region. To distinguish two different cervical N13, it is useful to detect not only the cervical pathology but also the symptomatic cervical cord compression level in patients with cervical myelopathy.

Adult↗

Structure formation and tearing of an MeV cylindrical electron beam in a laser-produced plasma.

The stability of a cylindrical, solid hot electron beam propagating in a high density plasma has been studied using a two-dimensional, hybrid Darwin code. The initially solid beam evolves into a hollow, annular beam due to the Weibel instability and generates strong magnetic fields on both sides of the annular ring. The annular structure subsequently breaks up into several beamlets via a mechanism similar to a tearing instability. It is found that the magnetic fields parallel to the direction of beam propagation also grow due to the tearing process.

Journal Article↗