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Biomedical subjects

M Naito

Publications and source records attributed to M Naito.

At least 19 recordsLinked to original sources

Fluorescence X-ray absorption spectroscopy using a Ge pixel array detector: application to high-temperature superconducting thin-film single crystals.

A Ge pixel array detector with 100 segments was applied to fluorescence X-ray absorption spectroscopy, probing the local structure of high-temperature superconducting thin-film single crystals (100 nm in thickness). Independent monitoring of pixel signals allows real-time inspection of artifacts owing to substrate diffractions. By optimizing the grazing-incidence angle theta and adjusting the azimuthal angle phi, smooth extended X-ray absorption fine structure (EXAFS) oscillations were obtained for strained (La,Sr)2CuO4 thin-film single crystals grown by molecular beam epitaxy. The results of EXAFS data analysis show that the local structure (CuO6 octahedron) in (La,Sr)2CuO4 thin films grown on LaSrAlO4 and SrTiO3 substrates is uniaxially distorted changing the tetragonality by approximately 5 x 10(-3) in accordance with the crystallographic lattice mismatch. It is demonstrated that the local structure of thin-film single crystals can be probed with high accuracy at low temperature without interference from substrates.

Algorithms↗

Dysregulated expression of P1 and P2 promoter-driven hepatocyte nuclear factor-4alpha in the pathogenesis of human cancer.

Hepatocyte nuclear factor-4alpha (HNF4alpha) exists in multiple isoforms that are generated by alternative promoter (P1 and P2) usage and splicing. Here we establish monoclonal antibodies (mAbs) for detecting P1 and P2 promoter-driven HNF4alpha, and evaluate their expression in normal adult human tissues and surgically resected carcinomas of different origins. Using immunohistochemical analysis, we demonstrate that, while P1 promoter-driven HNF4alpha is expressed in hepatocytes, small intestine, colon, kidney and epididymis, P2 promoter-driven HNF4alpha is expressed in bile duct, pancreas, stomach, small intestine, colon and epididymis. Altered expression patterns of P1 and P2 promoter-driven HNF4alpha were observed in gastric, hepatocellular and colorectal carcinomas. HNF4alpha was expressed in lung metastases from renal cell, hepatocellular and colorectal carcinoma but was not observed in lung tumours. The P1 and P2 promoter-driven HNF4alpha expression pattern of tumour metastases correlated with the primary site of origin. P1 promoter-driven HNF4alpha was also found in intestinal metaplasia of the stomach. These data provide evidence for the tissue distribution of P1 and P2 promoter-driven HNF4alpha at the protein level and suggest that HNF4alpha may be a novel diagnostic marker for metastases of unknown primary. We propose that the dysregulation of alternative promoter usage of HNF4alpha is associated with the pathogenesis of certain cancers.

Animals↗

Natural releases from contaminated groundwater, Example Reference Biosphere 2B.

Safety assessment is a tool which, by means of an iterative procedure, allows the evaluation of the performance of a disposal system and its potential impact on human health and the environment. Radionuclides from a deep geological disposal facility may not reach the surface environment until many tens of thousands of years after closure of the facility. The BIOMASS Programme on BIOsphere Modelling and ASSessment developed Examples of "Reference Biospheres" to illustrate the use of the methodology and to demonstrate how biosphere models can be developed and justified as being fit for purpose. The practical examples are also intended to be useful in their own right. The Example Reference Biosphere 2B presented here involves the consideration of alternative types of geosphere-biosphere interfaces and calculation of doses to members of hypothetical exposure groups arising from a wide range of exposure pathways within agricultural and semi-natural environments, but without allowing for evolution of the corresponding biosphere system. The example presented can be used as a generic analysis in some situations although it was developed around a relatively specific conceptual model. It should be a useful practical example, but the above numerical results are not intended to be understood as prescribed biosphere 'conversion factors'.

Adult↗

Aberrant promoter methylation in human DAB2 interactive protein (hDAB2IP) gene in gastrointestinal tumour.

The human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumour-suppressor gene inactivated by methylation in several cancers. In this study, we analysed the methylation and expression status of hDAB2IP in gastrointestinal tumours. The promoter region of hDAB2IP was divided into two regions (m2a and m2b) based on our previous report, and the methylation status was determined by bisulphite DNA sequencing in gastric cancer cell lines. The gene expression was semiquantified by real-time RT-PCR, and the results indicated that the m2b promoter region might be an authentic methylation-mediated key regulator of the gene expression. Based on the sequence data, we developed a methylation-specific PCR (MSP) for the m2a and m2b regions and applied it to the samples. Methylation-specific PCR revealed aberrant methylation in the m2a region in eight of 12 gastric cancer cell lines (67%), 16 of 35 gastric cancer tissues (46%) and 29 of 60 colorectal cancer tissues (48%), and in the m2b region in eight of 12 cell lines (67%), 15 of 35 gastric cancer tissues (43%) and 28 of 60 colorectal cancer tissues (47%). On the other hand, seven (12%) and 11 (19%) of 59 gastrointestinal nonmalignant mucosal specimens showed methylation in the m2a and m2b regions, respectively, suggesting that hDAB2IP methylation might play a causative role in carcinogenesis. The 5-aza-2'-deoxycytidine treatment restored the gene expression in the m2b-methylated cell lines, confirming that the methylation caused gene downregulation. We also examined the relationship between hDAB2IP methylation and the clinicopathological features in patients with primary tumours, and determined that methylation in the m2b region was associated with location of the tumour in the stomach. In summary, our results demonstrated that hDAB2IP methylation is frequently present in gastrointestinal tumours and that the resulting gene silencing plays an important role in gastrointestinal carcinogenesis.

Azacitidine↗

A clinical study of Japanese patients with ulcer induced by low-dose aspirin and other non-steroidal anti-inflammatory drugs.

BACKGROUND: The incidence and severity of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastro-duodenal ulcer have not been extensively studied in Japan. AIM: We performed a prospective study to clarify NSAIDs-induced gastro-duodenal injury, focusing especially on low-dose aspirin (L-A). METHODS: Two hundred and thirty-eight patients with bleeding peptic ulcers admitted to our hospital. History of taking NSAIDs and anti-ulcer drugs was obtained from all patients who underwent endoscopic examinations. The lesion scores of patients taking L-A were classified numerically from zero (no lesion) to five (ulcer). RESULTS: The NSAIDs were associated with 28.2% of hemorrhagic ulcers. The rates of patients using L-A, loxoprofen, diclofenac, and combination of two of these drugs were 27, 16, 10 and 9%, respectively. Co-administered anti-ulcer drugs were cytoprotective anti-ulcer drugs (27%), H2 receptor antagonists (16%), PPI (4%), and none (53%). In patients taking L-A, H2 receptor antagonists were used most frequently. The HP was positive in 63% of L-A-induced ulcer cases and in 69% of NSAIDs other than low-dose aspirin-induced ulcer cases. The lesion scores of patients taking L-A with H2 receptor antagonists or PPI were significantly lower than those of patients who were taking only L-A (P < 0.05). CONCLUSIONS: Approximately one-third of hospitalized patients with NSAIDs-induced hemorrhagic ulcer showed an association with L-A. Prospective randomized controlled trials including H2 receptor antagonists are required to establish preventive efforts aimed at L-A-induced gastro-duodenal injury.

Adult↗

Prostaglandin EP4 receptor agonist augments fixation of hydroxyapatite-coated implants in a rat model of osteoporosis.

The reduced stability of hydroxyapatite (HA)-coated implants in osteopenic conditions is considered to be a major problem. We therefore developed a model of a boosted cementless implantation in osteopenic rats.Twelve-week-old rats were either ovariectomised (OVX) or sham-operated (SO), and after 24 weeks plain or HA-coated implants were inserted. They were treated with either a prostaglandin EP4 receptor agonist (ONO-4819) or saline for one month. The EP4 agonist considerably improved the osteoporosis in the OVX group. Ultrastructural analysis and mechanical testing showed an improvement in the implant-bone attachment in the HA-coated implants, which was further enhanced by the EP4 agonist. Although the stability of the HA-coated implants in the saline-treated OVX rats was less than in the SO normal rats, the administration of the EP4 agonist significantly compensated for this shortage. Our results showed that the osteogenic effect of the EP4 agonist augmented the osteoconductivity of HA and significantly improved the stability of the implant-bone attachment in the osteoporotic rat model.

Animals↗

Effects of long-term treatment with mizoribine in patients with proliferative lupus nephritis.

AIM: Mizoribine (MZR) is a purine antimetabolic immunosuppressant agent that has few little severe adverse events. We studied whether maintenance therapy with MZR and prednisolone (PSL) in severe proliferative lupus nephritis patients could improve immunity, reduce proteinuria, prevent renal relapse, and reduce steroid dose. METHOD: Long-term maintenance therapy with MZR and PSL was evaluated in ten patients with biopsy-proven proliferative lupus nephritis. Patients with severe lupus nephritis, who had proteinuria of 0.5 g or more even after treatments with plasma exchange and/or pulse methyl prednisolone, were recruited. MZR at an average dose of 140 +/- 10 (100 - 200) mg was administered two to three times/day in combination with PSL. The average period for the MZR maintenance therapy was 89.7 +/- 5.5 (70 - 126) months. Urine protein excretion, serum hemolytic complement activity (CH50), C3, serum creatinine, general and biochemical blood examinations, anti-ds-DNA antibody were collected at each monthly medical examination. RESULTS: All patients were females, mean age 43.0 +/- 3.3 years. A significant decrease in proteinuria was noted two years after the combination therapy (p = 0.0016). Five patients experienced lupus nephritis relapse. Patients who did not experience relapses had their MZR combination therapy initiated earlier (p = 0.037) when compared with the patients who experienced relapses. Serum creatinine levels remained unchanged in all patients throughout treatment and follow-up, even during renal relapses. Levels of C3 and CH50 normalized as proteinuria decreased. None of the patients developed serious side effects during MZR treatment. A significant steroid-sparing effect was observed three years after initiating MZR (p = 0.0025). CONCLUSION: From our long-term observation, maintenance therapy with low-dose PSL combined with MZR can eliminate proteinuria and have steroid-sparing effect. Early initiation of the therapy can protect against renal relapses among severe proliferative lupus nephritis patients without serious side effects.

Adult↗

Expression of human coagulation factor VIII in adipocytes transduced with the simian immunodeficiency virus agmTYO1-based vector for hemophilia A gene therapy.

We demonstrate that transduction of adipocytes with a simian immunodeficiency virus agm TYO1 (SIVagm)-based lentiviral vector carrying the human coagulation factor VIII gene (SIVhFVIII) resulted in expression of the human FVIII transgene in vitro and in db/db mice in vivo. Cultured human adipocytes were transduced with the SIVagm vector carrying the GFP gene in a dose-dependent manner and transduction of adipocytes with SIVhFVIII resulted in efficient expression of human coagulation factor VIII (hFVIII; 320 +/- 39.8 ng/10(6) adipocytes/24 h) in vitro. Based upon successful transduction of adipocytes by SIV vectors carrying the lacZ gene in vivo in mice, the adipose tissue of db/db mice was transduced with SIVhFVIII. There was a transient appearance of human FVIII in mouse plasma (maximum 1.8 ng/ml) on day 11 after the injection. Transcripts of human FVIII transgene and human FVIII antigen also were detected in the adipose tissue by RT-PCR and immunofluorescence, respectively, on day 14. Emergence of anti-human FVIII antibodies 14 days after the injection of SIVhFVIII may explain the disappearance of human FVIII from the circulation. These results suggest that transduction of the adipocytes with vectors carrying the human FVIII gene may be potentially applicable for gene therapy of hemophilia A.

Adipocytes↗

Migration of primordial germ cells isolated from embryonic blood into the gonads after transfer to stage X blastoderms and detection of germline chimaerism by PCR.

1. The present study was carried out to determine whether primordial germ cells isolated from embryonic blood can enter the bloodstream and successfully migrate to the germinal ridges of recipient embryos after transfer to stage X blastoderms, and also whether they can differentiate into blood cells, as is suggested in mice. 2. Primordial germ cells were transfected in vitro by lipofection and then transferred to stage X blastoderms. The introduced GFP gene was efficiently expressed in the gonads of 6-d incubated embryos. 3. Freshly collected primordial germ cells were transferred to stage X blastoderms. The fate of the transferred primordial germ cells was traced by detecting the single nucleotide polymorphism in the D-loop region of the mitochondrial DNA in White Leghorn and Barred Plymouth Rock chickens used in this study. The transferred donor primordial germ cell-derived cells were detected in the gonads, but not in the blood cells, of 17-d incubated embryos by PCR. 4. This procedure for primordial germ cell manipulation could provide a novel method of producing germline chimaeric chickens. 5. In conclusion, our findings indicate that primordial germ cells isolated from embryonic blood can migrate to the germinal ridges of recipient embryos after being transferred to stage X blastoderms. Although these transferred primordial germ cells differentiated into germ cells, no differentiation into blood cells was observed.

Animals↗

Cementless total hip arthroplasty using an autograft of the femoral head for marked acetabular dysplasia: case series.

PURPOSE: To assess the short-term outcome of cementless total hip arthroplasty involving an autograft of the femoral head in Japanese patients. METHODS: Cementless total hip arthroplasty with autogenous bone block grafting was performed on 18 hips in 15 patients with marked acetabular dysplasia. The resected femoral head was used as a graft for the superior-lateral region of the true acetabulum. Clinical outcome was correlated with the placement of the acetabular component, as revealed in radiographs. RESULTS: The 13 women and 2 men had a mean age of 60.2 years (range, 37.0-73.0 years) at primary surgery and a mean follow-up duration of 3.3 years (range, 2.0-5.3 years). According to the classification of Crowe, 4 hips were in group I, 3 were in group II, one in group III, and 10 in group IV. The mean Harris Hip Score preoperatively was 45.7 (range, 19-69) and that at follow-up was 82.5 (range, 44-100). All 15 cases showed a good clinical outcome. There were no major intra-operative complications in this series. The grafted bones united in all patients. Two patients need surgical revision because the lateral insertion of the acetabular component resulted in loosening of it. CONCLUSION: Medial insertion of the acetabular component provides satisfactory short-term outcomes. Lateral insertion of the acetabular component during total hip arthroplasty should be avoided in patients with marked acetabular dysplasia.

Acetabulum↗

Total hip arthroplasty: the relationship between posterolateral reconstruction, abductor muscle strength, and femoral offset.

PURPOSE: To evaluate the relationship between posterolateral reconstruction, abductor muscle strength, and femoral offset following total hip arthroplasty. METHODS: Of 28 patients (56 limbs) we assessed, 12 underwent posterolateral reconstruction (reconstruction group) and 16 did not (non-reconstruction group). Isometric abductor muscle strength was measured with a handheld dynamometer. Each patient's muscle strength was converted into a force to body weight ratio, and this ratio was used in the comparisons. RESULTS: The reconstruction group showed a higher value in abductor muscle strength than the non-reconstruction group (p<0.05). Significant correlation between abductor muscle strength and femoral offset was found in the reconstruction group (p=0.016; r=0.674). CONCLUSION: Posterolateral reconstruction and appropriate reconstruction of femoral offset following total hip arthroplasty are important to improve the abductor muscle strength.

Aged↗

L-shaped caliper for limb length measurement during total hip arthroplasty.

The existing methods of assessing limb lengthening during total hip arthroplasty (THA) are prone to error because the measurements are not parallel to the limb lengthening axis. In order to address this, we designed a caliper to estimate limb lengthening during THA and evaluated its accuracy compared with our previous device, the straight caliper. Limb lengths were measured in 100 patients. The L-shaped caliper was used in 50 cases and the straight caliper in 50. The correlation between intra-operative and post-operative radiographic measurements was significantly improved using the L-shaped device (p < 0.0001, r = 0.934). This method was extremely accurate in predicting changes in limb length due to surgery.

Adult↗

Magnetic penetration depth measurements of Pr2-xCexCuO4-delta films on buffered substrates: evidence for a nodeless gap.

We report measurements of the inverse squared magnetic penetration depth, lambda(-2)(T), in Pr(2-x)Ce(x)CuO(4-delta) (0.115< or =x < or =0.152) superconducting films grown on SrTiO3 (001) substrates coated with a buffer layer of insulating Pr2CuO4. lambda(-2)(0), T(c), and normal-state resistivities of these films indicate that they are clean and homogeneous. Over a wide range of Ce doping, 0.124< or =x < or =0.144, lambda(-2)(T) at low T is flat: it changes by less than 0.15% over a factor of 3 change in T, indicating a gap in the superconducting density of states. Fits to the first 5% decrease in lambda(-2)(T) produce values of the minimum superconducting gap in the range of 0.29< or =Delta(min)/k(B)T(c)< or =1.01.

Journal Article↗

Transscaphoid-transtriquetral perilunate fracture dislocation: report of a case and review of the literature.

INTRODUCTION: A transscaphoid and transtriquetral perilunate fracture dislocation is fairly rare among the known cases of perilunate fracture dislocations, and the details of the initial treatment and outcome of this injury have never been reported. MATERIALS AND METHODS: A 21-year-old, right-handed man presented with fractures at the proximal third of the scaphoid and at the mid-body of the triquetrum with an associated dorsal perilunate dislocation after a fall onto his outstretched hand. Under general anesthesia, closed reduction was attempted with 3 kg of traction applied by means of finger traps. After anatomical reduction was achieved, percutaneous fixation was applied to both the triquetrum and scaphoid using cannulated screws. A short arm thumb spica splint was applied for 2 weeks, and part-time splinting was continued for an additional 3 weeks. The patient subsequently underwent 3 months of intensive range-of-motion and muscle-strengthening exercises. RESULTS: At the final follow-up examination 68 months after the initial operation, the arc of motion of the right wrist, 150 degrees (extension plus flexion arc), and grip strength, 41 kg, were 94% and 103% of the values for the unaffected wrist, respectively. Radiographs showed a bony union of the scaphoid and triquetrum, and no sign of avascular necrosis in the proximal scaphoid fragment, as well as other carpi. No midcarpal or radiocarpal degenerative arthritis was observed, and the normal carpal bone relationships were still maintained, with a scapholunate angle of 48 degrees and a scapholunate gap of 2 mm. CONCLUSION: We recommend closed reduction and percutaneous screw fixation of the scaphoid, as well as the triquetrum in this case, to minimize the interruption of the blood supply to the carpus and also to obtain rigid fixation during the procedure.

Accidental Falls↗

A hidden pseudogap under the 'dome' of superconductivity in electron-doped high-temperature superconductors.

The ground state of superconductors is characterized by the long-range order of condensed Cooper pairs: this is the only order present in conventional superconductors. The high-transition-temperature (high-T(c)) superconductors, in contrast, exhibit more complex phase behaviour, which might indicate the presence of other competing ground states. For example, the pseudogap--a suppression of the accessible electronic states at the Fermi level in the normal state of high-T(c) superconductors-has been interpreted as either a precursor to superconductivity or as tracer of a nearby ground state that can be separated from the superconducting state by a quantum critical point. Here we report the existence of a second order parameter hidden within the superconducting phase of the underdoped (electron-doped) high-T(c) superconductor Pr2-xCe(x)CuO4-y and the newly synthesized electron-doped material La2-xCe(x)CuO4-y (ref. 8). The existence of a pseudogap when superconductivity is suppressed excludes precursor superconductivity as its origin. Our observation is consistent with the presence of a (quantum) phase transition at T = 0, which may be a key to understanding high-T(c) superconductivity. This supports the picture that the physics of high-T(c) superconductors is determined by the interplay between competing and coexisting ground states.

Journal Article↗

Introduction of exogenous DNA into gonads of chick embryos by lipofection and electroporation of stage X blastoderms in vivo.

1. In order to introduce exogenous DNA into gonads of chick embryos, stage X blastoderms of freshly laid and unincubated eggs were transfected by lipofection and electroporation in vivo. 2. The introduced DNA, green fluorescence protein (GFP) gene, was efficiently expressed in the blastoderms incubated for 24 h (78.8%, 78/99). 3. The GFP gene was present in most of the embryonic bodies and extra-embryonic membranes died by d 10 of incubation, when analysed by polymerase chain reaction. On d 16 to 20 of incubation, the GFP gene was detected in 7.0 to 20.9% of embryos in the heart, liver, stomach and brain, but not in the sartorius muscle. For the gonads, the GFP gene was detected in 22.2% (6/27) of the testes and 6.3% (1/18) of the ovaries examined. 4. These results suggest that it is possible to introduce exogenous DNA into gonads of chick embryos by lipofection and electroporation of stage X blastoderms in vivo.

Animals↗

Physicians's reports on the impact of living wills at the end of life in Japan.

CONTEXT: A growing number of Japanese people have completed advance directives, especially living wills, even though there is no legislation recognising such documents and little empirical research on their impact on clinical care at the end of life in Japan. OBJECTIVES: To investigate physicians' attitudes about living wills and their experiences with patients who had completed a living will and later died. DESIGN: Self administered survey and qualitative study using open question and content analysis. SETTING: Japan. PARTICIPANTS: Physicians known to have cared for a patient who had presented a living will prior to death. MEASUREMENTS: The physician's response to receiving a living will, communication about the living will, the impact of the living will on clinical care, demographics, and their opinion on advance directives, especially living wills. MAIN RESULTS: Fifty five per cent of respondents approved of advance directives in general, and 34% had more opportunities to communicate with a patient and his/her family after receiving the living will. Sixty nine per cent of the physicians who received a living will did not, however, change their course of therapy as a consequence of receiving the living wills. Based on the analysis, we identified three areas of concern in the comments on living wills: (1) concerns relative to patients, physicians, and families; (2) social context, and (3) clinical and administrative concerns. The physicians raised various topics for discussion; they tended to describe the issues from a clinical perspective. CONCLUSIONS: Our identified areas of concern should prove helpful in better understanding the clinical and ethical implications of living wills in Japan.

Advance Directive Adherence↗