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Biomedical subjects

N Tanaka

Publications and source records attributed to N Tanaka.

At least 253 records · Page 14Linked to original sources

Variations in 5-fluorouracil concentrations of colorectal tissues as compared with dihydropyrimidine dehydrogenase (DPD) enzyme activities and DPD messenger RNA levels.

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in 5-fluorouracil (5-FU) catabolism. We measured DPD activities represented as DPD protein levels (units/mg protein) and the associated mRNA levels in tumorous and normal tissues from 40 colorectal cancer patients, and we studied the relation to 5-FU concentrations in the same samples after treatment with doxifluridine, a prodrug of 5-FU. DPD mRNA levels were also measured in biopsy samples before treatment for comparison with those in surgical samples. 5-FU concentrations in tumors were higher than those in normal tissues (P < 0.05) and were inversely associated with DPD protein levels (r = -0.463; P < 0.05). DPD activities in tumorous and normal tissues showed a significant correlation (r = 0.527; P < 0.01). DPD protein levels correlated with their mRNA levels detected by semiquantitative reverse transcription-PCR in tumor tissues (r = 0.740; P < 0.01). DPD mRNA levels in tumor biopsy specimens correlated with those in surgical specimens (r = 0.366; P < 0.05). These results suggest DPD activities in tumors to be predictive of 5-FU levels in colorectal cancer tissues and are reflected by DPD mRNA levels as measured by reverse transcription-PCR.

Antimetabolites, Antineoplastic↗

Impact of tacrolimus and bone marrow augmentation on intestinal allograft survival and intragraft cytokine expression in rats.

Effects of simultaneous bone marrow transplantation (BMT) with a short course of tacrolimus on a heterotopic small bowel transplantation (SBT) were tested in a high responder rat combination of ACI (RT1avl) to LEW (RTIl). Intestinal allograft survival and changes of intragraft cytokine expression by this treatment were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Only the treatment with donor specific BMT via portal vein plus a short course of tacrolimus (1.0 mg/Kg for 3 days) significantly prolonged allograft survival (mean +/- SD; 11.7 +/- 1.9 days), while the grafts were rejected at 4 to 8 days by other control treatments. More beneficial effect of donor type BMT via portal vein on allograft survival was achieved (19.0 +/- 2.2 days) by containing administration of a lower dose of tacrolimus (0.5 mg/Kg for 11 days). Both gene expression of IFN-gamma and infiltration of IFN-gamma-producing cells were strongly suppressed by this protocol, while tacrolimus treatment alone could not suppress IFN-gamma production. Tacrolimus treatment added with donor specific BMT down-regulated IL-12 and IFN-gamma transcript, resulted in a significant prolongation of intestinal allograft survival.

Animals↗

Biochemical and genetic analysis of the effects of amylose-extender mutation in rice endosperm.

Biochemical analysis of amylose-extender (ae) mutant of rice (Oryza sativa) revealed that the mutation in the gene for starch-branching enzyme IIb (BEIIb) specifically altered the structure of amylopectin in the endosperm by reducing short chains with degree of polymerization of 17 or less, with the greatest decrease in chains with degree of polymerization of 8 to 12. The extent of such change was correlated with the gelatinization properties of the starch granules, as determined in terms of solubility in urea solution. The ae mutation caused a dramatic reduction in the activity of BEIIb. The activity of soluble starch synthase I (SSI) in the ae mutant was significantly lower than in the wild type, suggesting that the mutation had a pleiotropic effect on the SSI activity. In contrast, the activities of BEI, BEIIa, ADP-Glc pyrophosphorylase, isoamylase, isoamylase, pullulanase, and Suc synthase were not affected by the mutation. Therefore, it is stressed that the function of BEIIb cannot be complemented by BEIIa and BEI. These results strongly suggest that BEIIb plays a specific role in the transfer of short chains, which might then be extended by SS to form the A and B(1) chains of amylopectin cluster in rice endosperm.

1,4-alpha-Glucan Branching Enzyme↗

[Whole-body ssFSE-IR MR imaging in the detection of bone metastases].

Preliminary studies were performed to evaluate the usefulness of whole-body MR imaging using the inversion recovery single shot fast spin echo (ssFSE-IR) sequence in the detection of bone metastases. Two sets of coronal ssFSE-IR images (ssSTIR: TI = 150, ssT1W: TI = 550) were obtained for four body segments without respiratory triggering or ECG/peripheral gating. In 8 patients with bone metastases, all lesions were easily detected on both sets of images; lesions showed high signal intensity on ssSTIR and markedly low signal intensity on ssT1W.

Adult↗

[Placement of the inferior vena cava filter proximal to the renal vein in a patient with left-sided inferior vena cava complicated by pulmonary embolism: a case report].

A 55-year-old man was admitted to our hospital complaining of dyspnea and chest pain. Transthoracic echocardiography showed dilation of the right ventricle. Chest computed tomography with contrast medium showed multiple emboli in the pulmonary arteries. Venography of the lower extremities showed multiple thrombi in the right popliteal vein and the presence of left-sided vena cava. This unusual case of left-sided vena cava was complicated by deep vein thrombosis due to hemostasis. A Greenfield filter was placed in the vena cava proximal to the right renal vein in a right internal jugular vein approach.

Humans↗

[Transarterial chemoembolization (TAE) with degradable starch microspheres (DSM) in advanced hepatocellular carcinoma].

This study was undertaken to evaluate the clinical utility of chemoembolization using degradable starch microspheres (DSM), which resolve in a short period in patients with advanced hepatocellular carcinoma (HCC). Twenty-one patients underwent DSM chemoembolization 24 times. After a mixture of iodized oil and epirubicin was injected into the hepatic arteries, the patients were embolized with DSM alone 16 times. In the other 8 times, embolization was done in one hepatic lobe with DSM and in the other hepatic lobe with gelatin sponge (GS). There was no major complication related to chemoembolization. Tumor response (complete, partial, and minor responses) was found in 46% of patients after TAE. Tumor recurrence was found in 64% of responders after a mean period of 2.0 months. The response rate was significantly higher when chemoembolization was performed using both DSM and GS than when it was done with DSM alone (63% vs 37%, p < 0.04). Although the response rate after DSM-TAE is low, its anticancer effect is reinforced when used as an adjuvant therapy of GS-TAE.

Aged↗

[Hepatic intra-arterial infusion chemotherapy using polymer-coated 2.9 Fr implantable catheter-port system--initial experience].

We developed a new 2.9 Fr implantable catheter-port system (reservoir) to perform arterial infusion chemotherapy in patients with unresectable liver tumors. This study was undertaken to evaluate the feasibility of placing this new reservoir system in patients in whom placement of a 5 Fr-reservoir system would seem to be difficult because of severe stricture, tortuosity or angulation of the hepatic artery. A new reservoir system was successfully implanted in 25 patients during 27 sessions. After a side hole was opened, a 2.9 Fr catheter was inserted in the distal hepatic artery or in the gastroduodenal artery in 24 sessions. The catheter tip was then fixed with coils to prevent catheter dislocation. In the other 3 sessions, a 2.9 Fr catheter was inserted without catheter fixation in the replaced right hepatic artery and a small sized collateral artery towards the liver. Arterial infusion chemotherapy was done without any trouble after 20 sessions. Catheter dislocation was found after 2 sessions in which the catheter tip was not fixed or inadequately fixed. Early arterial occlusion was found after placing a 2.9 Fr catheter in the replaced hepatic artery and the small sized-collateral artery after 4 sessions. In conclusion, although sequellae should be evaluated over a long-term period, implantation of a new 2.9 Fr reservoir system is technically feasible and useful in performing arterial infusion chemotherapy.

Aged↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1998 and March 1999].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982. This paper describes the results obtained in fiscal 1998 (from April 1998 to March 1999). The number of cases investigated as objectives was 225 for one year. A total of 429 strains (121 strains from primary infections and 308 strains from postoperative infections) were isolated from 183 cases (81.3% of total cases). In primary infections, the isolation rates of anaerobes and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes and Pseudomonas aeruginosa were higher than in primary infections. On the whole, among Gram-positive aerobes, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus with high frequency in isolation from postoperative infections. Among Gram-positive anaerobes, Peptostreptococcus spp. and Streptococcus spp. were predominantly isolated. Among Gram-negative aerobes, E. coli, P. aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were frequently isolated. Among Gram-negative anaerobes, Bacteroides fragilis group was the majority of isolates. In primary infections, the percentage of Gram-negative aerobes has gradually increased since fiscal 1995 or 1996 with these years as the turning point, while those of Gram-positive and Gram-negative anaerobes have gradually declined. In postoperative infections, the percentage of Gram-negative anaerobes has increased continuously since the mid-1980s. The percentage of MRSA among S. aureus rose to 89.7%, which was the highest level since the beginning of this study. The susceptibilities of B. fragilis, which did not show apparent changes, were recognized to have decreased against cephems in fiscal 1998. Among other bacteria in B. fragilis group, development of resistance to cephems has continued on a long-term basis since the mid-1980s. E. coli and K. pneuminiae have obviously not changed in susceptibilities, however, the susceptibilities of isolated strains in fiscal 1998 against high-generation cephems, oxacephems and monobactams have declined. We found neither vancomycin-resistant nor teicoplanin-resistant strains of S. aureus and Enterococcus spp.

Anti-Bacterial Agents↗

[Coronary artery dissection following angioplasty evaluated by fractional flow reserve: report of three cases].

Fractional flow reserve was measured in three patients with coronary artery dissection occurring after percutaneous coronary intervention. In Case 1, fractional flow reserve decreased from 0.88 to 0.73 and angiography showed coronary artery dissection 20 min after balloon angioplasty. In Case 2, angiography showed good results, but the fractional flow reserve decreased to a low value(0.69). Intravascular ultrasonography revealed dissection. In Case 3, angiography clearly showed dissection, but fractional flow reserve remained high(0.91). Stent implantation was performed in all three patients, but might not have been necessary in Case 3. Dissection with low or diminished fractional flow reserve value may cause a pressure gradient in the true lumen. Stent implantation is necessary in such cases. On the other hand, cases of dissection in which the fractional flow reserve value is maintained may also cause a pressure gradient in true lumen, but stent implantation may not be necessary. Fractional flow reserve measurements may be useful for the assessment of coronary artery dissection and evaluating the indications for stent implantation.

Aortic Dissection↗

Establishment and characterization of a human rectal neuroendocrine cell carcinoma in vitro.

Human colorectal neuroendocrine cell carcinoma ( NECC ) is uncommon. Treatment of the disease has not yet been established, and NECC of the colon and rectum behave clinically more aggressively than their exocrine counterparts, so the prognosis is generally worse. One reason for the lack of established treatment is that there are no model systems of this disease. There have been a few reports on cell lines from neuroendocrine tumors, because these tumors are difficult to culture, and there are even fewer reports on colorectal carcinoma cell lines with neuroendocrine features. We therefore attempted to establish a permanent cell line in order to investigate the biological behavior and treatment of NECC. The cell line we succeeded in culturing is called N-TAK1. Gastrin promotes the growth of gastrointestinal epithelial cells and also stimulates the growth of gastrointestinal cancers. Hormone-receptor antagonists restrict the growth of hormone-dependent tumors. The growth of colon cancer was promoted by the application of gastrin, whereas it was restricted by proglumide, which is known to be a gastrin receptor antagonist. We demonstrated that gastrin has a stimulatory effect on the growth of N-TAK1 cells and that it could be detected by immunohistochemistry in the cells. We also showed that proglumide inhibited the growth effect of gastrin.

Animals↗

The effect of disc degeneration and facet joint osteoarthritis on the segmental flexibility of the lumbar spine.

STUDY DESIGN: A biomechanical and imaging study of human cadaveric spinal motion segments. OBJECTIVE: To investigate the effect of both disc degeneration and facet joint osteoarthritis on lumbar segmental motion. SUMMARY OF BACKGROUND DATA: Spinal degeneration includes the osteoarthritic changes of the facet joint as well as disc degeneration. Disc degeneration has been reported to be associated with spinal motion. The association of facet joint osteoarthritis with lumbar segmental motion characteristics and the combined influence of disc degeneration and facet osteoarthritis has not yet been investigated. METHODS: A total of 110 lumbar motion segments (52 female, 58 male) from 44 human lumbar spines were studied (mean age = 69 years). Magnetic resonance images were used to assess the disc degeneration from Grade I (normal) to Grade V (advanced) and the osteoarthritic changes in the facet joints in terms of cartilage degeneration, subchondral sclerosis, and osteophytes. Disc height, endplate size, and facet joint orientation and width also were measured from the computed tomographic images. Rotational movements of the motion segment in response to the flexion, extension, lateral bending, and axial rotational moments were measured using a three-dimensional motion analysis system. RESULTS: Female motion segments showed significantly greater motion (lateral bending: P < 0. 001, flexion: P < 0.01, extension: P < 0.05) and smaller endplate size (P < 0.001) than male ones. The segmental motion increased with increasing severity of disc degeneration up to Grade IV, but decreased in both genders when the disc degeneration advanced to Grade V. In male segments, the disc degeneration-related motion changes were significant in axial rotation (P < 0.001), lateral bending (P < 0.05), and flexion (P < 0.05), whereas female segments showed significant changes only in axial rotation (P < 0.001). With cartilage degeneration of the facet joints, the axial rotational motion increased, whereas the lateral bending and flexion motion decreased in female segments. In male segments, however, motion in all directions increased with Grade 3 cartilage degeneration and decreased with Grade 4 cartilage degeneration. Subchondral sclerosis significantly decreased the motion (female: axial rotation, P < 0. 05; extension, P < 0.05 vs.- male:flexion,P < 0.05). Severity of osteophytes had no significant association with the segmental motion. CONCLUSION: Axial rotational motion was most affected by disc degeneration, and the effects of disc degeneration on the motion were similar between genders. Facet joint osteoarthritis also affected segmental motion, and the influence differed for male and female spines. Further studies are needed to clarify whether the degenerative process of facet joint osteoarthritis differs between genders and how facet joint osteoarthritis affects the stability of the spinal motion segment.

Cadaver↗

Intra-tumoral injection of doxorubicin (adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects.

Encapsulation of doxorubicin (Adriamycin) in liposome (LipADM) augments the anti-tumor effects of the drug and reduces side effects such as cardiotoxicity. However, it does not always enhance anti-tumor effects because of entrapment by the reticuloendothelial system. In this study, we investigated the anti-tumor effect of LipADM injected directly into the tumor to augment tumor targeting. LipADM (7.5 mg/kg body weight), the same concentration as free ADM (FADM), was injected percutaneously or i.v. into 7-day-old established Meth-A tumors in mice. Mock liposome was injected percutaneously into tumors of control mice. Mean relative tumor weights of the 5 groups on day 15 were as follows: intra-tumoral injection of LipADM, 2.92 +/- 1.09; intra-tumoral injection of FADM, 6.99 +/- 2.92; i.v. injection of LipADM, 11.07 +/- 7.95; i.v. injection of FADM, 11.80 +/- 6.55; control, 23.94 +/- 9.03. Mean survival times were as follows: intra-tumoral injection of LipADM, 46.2 +/- 11.0 days; FADM, 34.6 +/- 9.6 days; mock control, 30.2 +/- 4.8 days. Histological examination showed no tissue damage at the site of s.c. injection of LipADM. ADM concentrations in tumor tissues after intra-tumoral injection were persistently high in the LipADM-treated group. Our results indicate that direct injection of LipADM into the tumor is therapeutically useful by producing persistently high concentrations of ADM in the target tissue, with few local and systemic side effects.

Animals↗

Contribution of CD95 ligand-induced neutrophil infiltration to the bystander effect in p53 gene therapy for human cancer.

Clinical trials of adenoviral p53 gene therapy provide the evidence that the bystander effect induced by the wild-type p53 gene transfer on adjacent tumor cells contributes to tumor progression; its mechanism, however, remains uncharacterized. We report in this work that injection of adenovirus expressing the human wild-type p53 gene (Ad5CMVp53) into established human colorectal tumors in nu/nu mice resulted in CD95 ligand (CD95L) overexpression, followed by a massive neutrophil infiltration. Culture supernatants of human colorectal cancer cells infected with Ad5CMVp53 exhibited a potent chemotactic activity against murine polymorphonuclear neutrophils, which could be abolished by the anti-CD95L mAb (NOK-1). In vivo cell depletion experiments indicated that neutrophils were in part responsible for the antitumor effect of the Ad5CMVp53 infection. Our data directly suggest that overexpression of CD95L by the wild-type p53 gene transfer induces neutrophil infiltration into human colorectal tumors, which may play a critical role in the bystander effect of p53 gene therapy.

Adenoviruses, Human↗

Flagellin from an incompatible strain of Pseudomonas avenae induces a resistance response in cultured rice cells.

The host range of Pseudomonas avenae is wide among monocotyledonous plants, but individual strains can infect only one or a few host species. The resistance response of rice cells to pathogens has been previously shown to be induced by a rice-incompatible strain, N1141, but not by a rice-compatible strain, H8301. To clarify the molecular mechanism of the host specificity in P. avenae, a strain-specific antibody that was raised against N1141 cells and then absorbed with H8301 cells was prepared. When a cell extract of strain N1141 was separated by SDS-polyacrylamide gel electrophoresis and immunostained with the N1141 strain-specific antibody, only a flagellin protein was detected. Purified N1141 flagellin induced the hypersensitive cell death in cultured rice cells within 6 h of treatment, whereas the H8301 flagellin did not. The hypersensitive cell death could be blocked by pretreatment with anti-N1141 flagellin antibody. Furthermore, a flagellin-deficient N1141 strain lost not only the induction ability of hypersensitive cell death but also the expression ability of the EL2 gene, which is thought to be one of the defense-related genes. These results demonstrated that the resistance response in cultured rice cells is induced by the flagellin existing in the incompatible strain of P. avenae but not in the flagellin of the compatible strain.

Amino Acid Sequence↗

Pressure effect on the conformational fluctuation of apomyoglobin in the native state.

We have investigated the effect of pressure on fluctuations of the native state of sperm whale apomyoglobin (apoMb) by H/D exchange, fluorescence, and limited proteolysis. The results from intrinsic fluorescence showed that a large fraction of apoMb molecules is in the native conformation in the pressure range from 0.1 to 150 MPa at 293 K and pH 6.0. The H/D exchange of protons of the individual backbone amino acids in this pressure range was monitored by NMR. The rate of H/D exchange was enhanced at high pressure, with the protection factors for some residues decreasing by factors of more than 100 compared to the values at 0.1 MPa. The amplitude of the decrease of the protection factor varied among the individual amino acids on the same secondary structure unit. This result suggests that H/D exchange in apoMb is explained best by the penetration model, in which solvent penetrates into the protein matrix via small motions. The result from limited proteolysis under high pressure showed that a pressure increase does not induce local unfolding of the secondary structure units of apoMb. Conformational fluctuations much smaller than local unfolding evidently provide pathways for water to diffuse into the protein interior, and are enhanced by an increase of pressure.

Animals↗

The receptor for advanced glycation end products is induced by the glycation products themselves and tumor necrosis factor-alpha through nuclear factor-kappa B, and by 17beta-estradiol through Sp-1 in human vascular endothelial cells.

The binding of advanced glycation end products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. Here we show that AGE, tumor necrosis factor-alpha (TNF-alpha), and 17beta-estradiol (E(2)) up-regulated RAGE mRNA and protein levels in human microvascular endothelial cells and ECV304 cells, with the mRNA stability being essentially invariant. Transient transfection experiments with human RAGE promoter-luciferase chimeras revealed that the region from nucleotide number -751 to -629 and the region from -239 to -89 in the RAGE 5'-flanking sequence exhibited the AGE/TNF-alpha and E(2) responsiveness, respectively. Site-directed mutation of an nuclear factor-kappaB (NF-kappaB) site at -671 or of Sp-1 sites at -189 and -172 residing in those regions resulted in an abrogation of the AGE/TNF-alpha- or E(2)-mediated transcriptional activation. Electrophoretic mobility shift assays revealed that ECV304 cell nuclear extracts contained factors which retarded the NF-kappaB and Sp-1 elements, and that the DNA-protein complexes were supershifted by anti-p65/p50 NF-kappaB and anti-Sp-1/estrogen receptor alpha antibodies, respectively. These results suggest that AGE, TNF-alpha, and E(2) can activate the RAGE gene through NF-kappaB and Sp-1, causing enhanced AGE-RAGE interactions, which would lead to an exacerbation of diabetic microvasculopathy.

Blotting, Western↗