Biomedical subjects

A Inoue

Publications and source records attributed to A Inoue.

At least 55 records · Page 3Linked to original sources

PubMed2001

Cell-free translation reconstituted with purified components.

We have developed a protein-synthesizing system reconstituted from recombinant tagged protein factors purified to homogeneity. The system was able to produce protein at a rate of about 160 microg/ml/h in a batch mode without the need for any supplementary apparatus. The protein products were easily purified within 1 h using affinity chromatography to remove the tagged protein factors. Moreover, omission of a release factor allowed efficient incorporation of an unnatural amino acid using suppressor transfer RNA (tRNA).

Amino Acids↗

PubMed2001

S1 proteins C2 and D2 are novel hnRNPs similar to the transcriptional repressor, CArG box motif-binding factor A.

S1 proteins A-D are liberated from thoroughly washed nuclei by mild digestion with DNase I or RNase A, and extracted selectively at pH 4.9 from the reaction supernatants. Here, we characterized the S1 proteins, focusing on protein D2, the most abundant S1 protein in the rat liver, and on protein C2 as well. Using a specific antibody, McAb 351, they were shown to occur in the extranucleolar nucleoplasm, and to be extracted partly in the nuclear soluble fraction. We demonstrate that the S1 proteins in this fraction exist constituting heterogeneous nuclear ribonucleoproteins (hnRNPs), through direct binding to hnRNAs, as revealed by centrifugation on density gradients, immunoprecipitation, and UV cross-linking. In hnRNPs, protein D2 occurred at nuclease-hypersensitive sites and C2 in the structures that gave rise to 40 S RNP particles. By microsequencing, protein D2 was identified with a known protein, CArG box motif-binding factor A (CBF-A), which has been characterized as a transcriptional repressor, and C2 as its isoform protein. In fact, CBF-A expressed from its cDNA was indistinguishable from protein D2 in molecular size and immunoreactivity to McAb 351. Thus, the present results demonstrate that S1 proteins C2 and D2 are novel hnRNP proteins, and suggest that the proteins C2 and D2 act in both transcriptional and post-transcriptional processes in gene expression.

Amino Acid Sequence↗

PubMed2001

Inhibition of thyroid hormone binding to the nuclear receptor by mobilization of free fatty acids.

Through binding to its nuclear receptor (TR), thyroid hormone (T3) activates the expression of the thyroid hormone-responsive genes that are essential for the regulation of energy consumption. Previously, we found that free fatty acids (FFAs) and their CoA esters strongly inhibited the binding of T3 to its nuclear receptor in vitro. In the present study, we have examined the physiological relevance of this inhibitory mechanism. TRs in isolated nuclei and in a solubilized free form were half-maximally inhibited with oleic acid at 120 and 2.8 microM, respectively. The lower sensitivity of the nuclear TR as compared with free TR was attributed to the nuclear envelope and the association of TR with chromatin. Among TRs in chromatin, those in the transcriptionally active chromatin exhibited the highest sensitivities to FFAs and were inhibited half-maximally by oleic acid at 10 microM. While the plasma concentration of FFAs in total was 0.4 to 1 mM, their nuclear concentration was about 5 microM. Thus, the sensitivities of TRs in active chromatin and in solubilized form were at physiological levels with respect to the nuclear FFA concentration. We further examined the effect of FFA mobilization on the T3-binding to TR in animals. Nuclear T3-binding was significantly inhibited when plasma and cellular FFAs were increased by norepinephrine in vivo. The increase in cellular FFAs and the TR-inhibition were well correlated, and much larger in the heart than in the liver and kidney. These results suggest that TR is negatively controlled by increased FFAs in a tissue-dependent manner.

Animals↗

PubMed2001

Evaluation of beta-blocker therapy in patients with dilated cardiomyopathy--Clinical meaning of iodine 123-metaiodobenzylguanidine myocardial single-photon emission computed tomography.

BACKGROUND: Patients with heart failure show signs of cardiac sympathetic dysfunction such as elevation of blood norepinephrine (NE) level, as a result of reduction in the number of sympathetic nerves, decrease in myocardial NE content, accelerated NE turnover or spillover of NE, and NE reuptake disorder at sympathetic nerve endings. In dilated cardiomyopathy (DCM), iodine 123-metaiodobenzylguanidine (MIBG) used clinically as a tracer for imaging of the sympathetic function was found to be useful in evaluation of severity and prognosis. METHODS AND RESULTS: A total of 143 (123)I-MIBG myocardial single-photon emission computed tomography (SPECT) images were taken at successive intervals on 58 patients with DCM (mean age 54 +/- 11 years), as well as before and after therapy to determine the severity of DCM and the therapeutic effect of beta-blocker. Patients were divided into group A (n = 20), in which left ventricular ejection fraction (LVEF) improved by 10% or more within 6 months after the administration of beta-blocker, and group B (n = 20), in which there was less than a 10% change in LVEF. After (123)I-MIBG myocardial SPECT was taken, the washout rate for the entire left ventricle was calculated from early and delayed images. The estimations of extent score and severity score were based on the polar map prepared from short axial images taken from 17 healthy volunteers (mean age 35 +/- 5 years). There was a significant correlation between LVEF and (123)I-MIBG findings (extent score, severity score, and washout rate) obtained before and after beta-blocker therapy. After beta-blocker therapy, LVEF and (123)I-MIBG findings significantly improved in group A. On the other hand, no change occurred in (123)I-MIBG findings in group B. There was no significant difference in LVEF between group A (32.1% +/- 8.0%) and group B (29.5% +/- 7.2%). Also, there was no significant difference in the washout rate between group A (54.4% +/- 10.9%) and group B (52.9% +/- 7.2%). Comparison of (123)I-MIBG images before beta-blocker therapy of group A and group B revealed that the extent score (26.5 +/- 16.0 vs 44.5 +/- 21.1, respectively; P <.01) and the severity score (24.9 +/- 21.9 vs 58.2 +/- 35.2, respectively; P <.01) on the basis of the early (123)I-MIBG image was significantly lower for group A. CONCLUSIONS: From the above findings, patients with DCM in which (123)I-MIBG uptake is high on early images were expected to show improvement in cardiac function by beta-blocker therapy. Findings also suggested that (123)I-MIBG was useful for examining the severity of DCM, determining the applicability of beta-blocker therapy, estimating the maintenance dosage of beta-blocker, and evaluating prognosis.

3-Iodobenzylguanidine↗

PubMed2001

Recent advances in the chemotherapy of non-small cell lung cancer.

Chemotherapeutic regimens containing new anticancer agents in combination with cisplatin and carboplatin have been demonstrated to be equivalently active against advanced non-small cell lung cancer. The choice of a chemotherapeutic regimen depends on differences in time to progression, response rate, toxicity profile, cost and symptom relief. Several other strategies, such as three-drug combinations, sequential use of a third drug, weekly administration, etc., have been evaluated to improve the chemotherapeutic effect. The sequencing of the human genome may permit targeting of specific abnormalities related to each lung cancer with target-based drugs. This should increase the possibility of application of individualized therapy and, we would hope, improve survival.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

A dose escalation study of paclitaxel and carboplatin in untreated Japanese patients with advanced non-small cell lung cancer.

BACKGROUND: The combination of paclitaxel (225 mg/m(2), 3-h infusion) and carboplatin (area under the curve 6) is widely used for non-small cell lung cancer in the USA. In Japan, however, the recommended dose for single-use paclitaxel in 3-h infusion is 210 mg/m(2) and the optimal dose of this agent in combination with carboplatin has not been established. This dose escalation study was designed to determine the maximum tolerated dose of paclitaxel in 3-h infusion plus carboplatin at a fixed dose of area under the curve 6 for Japanese patients with advanced, untreated non-small cell lung cancer. METHODS: Between October 1999 and May 2000, 19 patients were enrolled and 18 of these patients were evaluable for toxicity. Chemotherapy consisted of carboplatin area under the curve 6 and an escalated dose of paclitaxel on day 1 every 3-4 weeks. The initial dose of paclitaxel was 175 mg/m(2) and was increased by 25 mg/m(2) at each dose level. RESULTS: Neutropenia was the major toxicity observed, but was not dose related. Febrile neutropenia was not observed. No grade 3 or more peripheral neuropathy, myalgia or arthralgia was reported. The maximum tolerated dose was not determined even at the highest paclitaxel dose level (225 mg/m(2)) in this study. Partial responses were observed in six of the 19 patients (31.6%). CONCLUSION: We conclude that paclitaxel at 225 mg/m(2) in 3-h infusion and carboplatin area under the curve 6 can safely be given to Japanese patients with non-small cell lung cancer.

Adult↗

PubMed2001

A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer.

BACKGROUND: A combination of cisplatin and vinorelbine chemotherapy is effective in cases of advanced non-small cell lung cancer, but the optimum administration schedule for both drugs has not yet been defined. The aim of this study was to determine the maximum dose of vinorelbine that can be tolerated while receiving a fixed dose of cisplatin every 3 weeks and to observe the response in Japanese patients with advanced non-small cell lung cancer who had not previously received chemotherapy. METHODS: Cisplatin was given at a dose of 80 mg/m2 on day 1. Vinorelbine was administered on days 1 and 8 at a starting dose of 25 mg/m2 that was then increased by 5 mg/m2 increments. This treatment was repeated every 3 weeks. RESULTS: Twenty-one patients received a total of 54 chemotherapy cycles consisting of three different vinorelbine dosages. Toxicity and efficacy were evaluated in all of the patients. The main dose-limiting toxicity was neutropenia. Grades 3-4 leukopenia and neutropenia were observed in 57% and 86% of all cycles, respectively. These conditions were reversible and did not result in death from toxicity. The most severe non-hematological toxicity symptom was a grade 3 infection and reaction at the site of injection. The maximum tolerated dose of vinorelbine was 35 mg/m2. The objective response was noted in one of six patients at dose level 1, in four of 12 patients at dose level 2 and in two of three patients at dose level 3. CONCLUSION: The recommended doses were 80 mg/m2 for cisplatin and 30 mg/m2 for vinorelbine. The combination of cisplatin and vinorelbine repeated every 3 weeks is well tolerated and has shown promising anti-tumor activity against non-small cell lung cancer.

Adult↗

PubMed2001

Interleukin-1-induced subacromial synovitis and shoulder pain in rotator cuff diseases.

OBJECTIVE: To determine the relationship between the expression of interleukin-1beta (IL-1beta) and IL-1 receptor antagonists (IL-1ra) in the subacromial bursa and shoulder pain in rotator cuff diseases. METHODS: Synovial specimens were analysed using various methods including reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and in situ RT-PCR. Thirty-nine patients with rotator cuff diseases were candidates. The degree of their shoulder pain was evaluated using a visual analogue scale. RESULTS: The mRNA expression levels of the cytokines were significantly correlated with the degree of pain [IL-1beta: r=0.782; secreted IL-1ra (sIL-1ra): r=0.756; intracellular IL-1ra (icIL-1ra): r=0.806, P<0.001, respectively]. The combined results of immunohistochemistry and in situ RT-PCR analysis indicated that both synovial lining and sublining cells produce IL-1beta, while synovial lining cells predominantly produce icIL-1ra and sublining cells secrete sIL-1ra. CONCLUSIONS: The differential regulation of the two forms of IL-1ra mRNAs may play an important role in shoulder pain in rotator cuff diseases, regulating IL-1-induced subacromial synovitis.

Adult↗

PubMed2001

Nanocrystallization of the Fd3m Ti2Ni-type phase in Hf-based metallic glasses.

Three ternary and four quaternary hafnium-based alloys have been rapidly solidified, and the devitrification of the resultant metallic glasses has been studied to evaluate the influence of composition on the products. The formation of metastable and stable Fd3m (Pearson symbol cF96) Ti2Ni was evident whenever the alloy composition in the stable equilibrium diagrams showed this phase. The replacement of nickel by iron led to the appearance of this phase in preference to the icosahedral quasicrystal. Several common features of the amorphous alloys that form either nanoscale icosahedral or cF96 Ti2Ni-type phases on devitrification are discussed and summarized.

Alloys↗

PubMed2001

Strategy for modulation of central dopamine transmission based on the partial agonist concept in schizophrenia therapy.

The dopamine system is known to be closely involved in brain neuronal dysfunction and in diseases such as Parkinson's disease, Tourette's syndrome, attention deficit hyperactive disorder, generation of pituitary tumors and schizophrenia. According to the classical dopamine hypothesis on the pathology of schizophrenia, conventional antipsychotics has D2 dopamine receptor antagonistic profiles. However, the use of typical antipsychotics has several limitations; that is, some patients do not respond to them, they can even worsen negative symptoms, and they can provoke unacceptable extrapyramidal and endocrine side effects. To produce effective antipsychotics with reduced side effects, partial agonists to D2 dopamine receptors (D2 receptors) have been developed. Despite the effectiveness of partial agonists for pre- and postsynaptic D2 receptors, administration of such drugs results in inconsistent clinical effects to ameliorate the symptoms of schizophrenia. Thus, strategies for obtaining ideal effective antipsychotics with reduced side effects are considered in this short review with respect to the intrinsic efficacies and affinities of the partial agonists, based on the partial agonist concept.

Antipsychotic Agents↗

PubMed2001

Fit and dimensional changes of cast CP titanium crowns fabricated using sintered molds.

The present study was undertaken to evaluate the clinical applicability of cast CP titanium crowns fabricated with sintered molds. To this end, the dimensional changes and accuracy of fit of cast CP titanium crowns, manufactured under varying mold firing temperatures, were examined. Molds were fired at 7 temperatures. The outer height of the crown and outer width of the occlusal surface decreased under all sets of firing conditions. The outer width of the cervical part tended to increase at firing temperatures of 1,200, 1,300 and 1,400 degrees C. The inner widths of the occlusal surface and cervical part tended to increase under all sets of firing conditions. In the analysis of the fit of crowns, floating (gained latitude) was observed under all sets of conditions. However, the amount of floating was significantly smaller when the firing temperature was 1,200, 1,300 or 1,400 degrees C than when it was 800, 900, 1,000 or 1,100 degrees C.

Analysis of Variance↗

PubMed2001

[Prediction of effect of beta-blocker therapy in patients with dilated cardiomyopathy by using 123I-BMIPP, 123I-MIBG scintigraphy].

We investigated prediction of the efficacy of beta-blocker therapy in patients with dilated cardiomyopathy (DCM) by using myocardial scintigraphy with 123I-BMIPP (BMIPP) and 123I-MIBG (MIBG). Thirty-seven patients with DCM were examined by myocardial scintigraphy with BMIPP and MIBG before beta-blocker therapy. Patients were classified into two groups, based on whether they improved > 10% of the left ventricular ejection fraction (LVEF) (improved group, n = 21) or not (unimproved group, n = 16). The extent and severity score of BMIPP for the improved group was significantly lower (p < 0.001) than that for unimproved group. It has been suggested that BMIPP is useful in evaluating the prediction of efficacy of beta-blocker therapy in patients with DCM.

3-Iodobenzylguanidine↗

PubMed2001

Comparison of the responses of global tests of coagulation with molecular markers of neutrophil, endothelial, and hemostatic system perturbation in the baboon model of E. colisepsis--toward a distinction between uncompensated overt DIC and compensated non-overt DIC.

This study correlates changes in neutrophilic activity and endothelial injury with markers of hemostatic activity following the infusion of increasing concentrations of E. coli organisms. It focuses on the hemostatic response as a marker of microvascular injury and uses the response to increasing concentrations of E. coli to refine our definition of disseminated intravascular coagulation (DIC) and distinguish between a compensated (non-overt DIC) and uncompensated (overt DIC) response. We observed that the global coagulation tests reflected activation of the hemostatic system in a dose dependent manner (overt DIC) in the early phases (T+2 to 6 h) of the response to increasing concentrations of E. coli, but that they failed to do so in the late phases (T+ 24 to 48 h). We observed that molecular markers, soluble thrombomodulin and elastase, unlike thrombin/antithrombin and plasmin/antiplasmin complexes, remained elevated out to T+24 to 48 h indicating endothelial injury that persists beyond the initial inflammatory insult in compensated as well as uncompensated DIC.

Animals↗

PubMed2001

[A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system].

AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions.

Aged↗

PubMed2001

[Evaluation of the new pump for home parenteral nutrition Terumo Cafty].

This study was undertaken to evaluate the usefulness of 'Cafty' which is a new infusion pump system for administering home parenteral nutrition (HPN), recently launched by Terumo Corporation. We used 'Cafty' in two patients and found it has more advantages than the existing pump with regard to the following points: 1. Cafty is provided with a display and alarms that indicate pump troubles such as emptiness, occlusion or mis-operation. 2. It is easier to carry because of its smaller size (width 80 mm x length 132 mm x thickness 33 mm) and its lighter weight (320 g). 3. While Cafty operation using a cassette-type tubing and plain control panel to simpler the flow rate accuracy is not reduced. In conclusion, Cafty is better than the existing HPN pump from the viewpoint of safety, portability and easiness.

Adolescent↗

PubMed2000

Identification of a Free Non-tryptophan Fluorophore in Water-soluble Fraction of Human Brunescent Cataractous Lens Nucleus.

Purpose: We previously reported that a unique free fluorophore (Fl-Glc), presumably a beta-glucoside, is particularly abundant in human brunescent cataractous lens nuclei. Our preliminary experiments indicated that incubation of low-molecular weight (MW) fraction of non-brunescent lens nuclei causes an increase in a particular fluorophore (Fl-X). This study was undertaken to compare the Fl-Glc with the Fl-X and subsequently to identify the Fl-X.Methods: Experiment (1) The purified Fl-X and its beta-glucosidase digest (aglycon) were compared with the Fl-Glc and its aglycon, respectively, by high-performance liquid chromatography (HPLC). Experiment (2) i) The Fl-X and its aglycon were analysed by liquid chromatography/mass spectrometry (LC/MS). ii) Authentic xanthurenic acid was analysed by HPLC and LC/MS.Results: Experiment (1) The retention times of the Fl-X and the Fl-Glc exactly coincided. The fluorescence peaks of both disappeared after beta-glucosidase treatment. Experiment (2) i) LC/MS results suggested that the MWs of the Fl-X and its aglycon were 367 and 205, respectively. ii) HPLC and LC/MS results for xanthurenic acid (MW = 205) were exactly the same as those for the aglycon of the Fl-X.Conclusions: The Fl-Glc and the Fl-X are identifical, and the Fl-X (= Fl-Glc) is a glucoside of xanthurenic acid.

Journal Article↗

PubMed2000

Effect of interferon therapy on the incidence of hepatocellular carcinoma and mortality of patients with chronic hepatitis C: a retrospective cohort study of 738 patients.

The effect of interferon on the long-term clinical outcome of patients with chronic hepatitis C remains unclear. This study included 594 patients with chronic hepatitis C who received interferon-alpha therapy (Interferon group) and 144 patients with chronic hepatitis C who did not receive interferon (Control group). The patients in the Interferon group were classified into the following three groups based on the response of the serum aminotransaminase level of the patient during and after completion of the therapy protocol: sustained responders (n = 175), transient responders (n = 165), and non-responders (n = 254). The age, sex, serum aminotransaminase level, platelet count, histological staging, hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted with the Cox proportional hazards model. The length of follow-up for assessment of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9 months in the Interferon group and 67.7 +/- 28.7 months in the Control group. Multivariate analysis showed that interferon therapy decreased the risk for developing HCC by 48% compared with that in the Control group (P = 0.064). The older the age, being male, having a low platelet count, and higher histological stage were independent factors associated with the development of HCC. The hazard rate ratio for development of HCC in the sustained responders, transient responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04-0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively. During follow-up, 18 patients in the Interferon group died (10 from liver-related diseases) and 17 patients in the Control group died (10 from liver-related diseases). No sustained responder or transient responder in the Interferon group died of liver-related disease. The cumulative survival rates of the Interferon and Control groups were nearly identical during the first 5 years following diagnosis. Thereafter, the cumulative survival rate of the Control group declined, resulting in an 8-year survival rate in the Interferon and Control groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the survival analysis of those who had died of liver disease: the 8-year survival rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0. 32). Our study demonstrated that interferon therapy significantly lowered the incidence of HCC among patients with chronic hepatitis C who showed sustained normalization and among patients who showed transient normalization of the serum aminotransferase level after completion of interferon therapy. The survival analyses and determination of cause of death suggested that interferon therapy improves the long-term survival of chronic hepatitis C patients who respond to this therapy, possibly by decreasing mortality from liver-related diseases.

Antiviral Agents↗

PubMed2000

Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene.

Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We constructed a recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the sensitivity to all six drugs regardless of the cellular p53 status, and a synergism was observed by the isobolic method in combination studies (D<1). We conclude that our strategy using adenoviral mediated p53 gene transfer to cancer cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an improvement of lung cancer chemotherapy.

Adenoviruses, Human↗