Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial.
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Condoms↗
Biomedical subjects
Kenji Maeda
Publications and source records attributed to Kenji Maeda.
Dynamic coordination polymers with 4,4'-oxybis(benzoate): reversible transformations of nano- and nonporous coordination frameworks responding to present solvents.
Reversible construction of a nanoporous framework from a nonporous framework has been found in the zinc(II) coordination polymer with 4,4'-oxybis(benzoate) (oba). [Zn(2)(oba)(2)(dmf)(2)].2DMF (1), which has 1 nm scale channels, transforms to the nonporous coordination polymer [Zn(oba)(H(2)O)] (2) with the loss of the open framework. Compound 2 on treatment with DMF reversibly yields nanoporous compound 1.
Benzoates↗
A new redox-active coordination polymer with cobalticinium dicarboxylate.
A new two-dimensional coordination polymer with cobalticinium 1,1'-dicarboxylate (ccdc) incorporated in the framework has been prepared, the ccdc functioning as unique monoanionic dicarboxylate ligands. The compound shows a high redox activity based on the ccdc units.
Journal Article↗
Cy5 maleimide labelling for sensitive detection of free thiols in native protein extracts: identification of seed proteins targeted by barley thioredoxin h isoforms.
Barley thioredoxin h isoforms HvTrxh1 and HvTrxh2 differ in temporal and spatial distribution and in kinetic properties. Target proteins of HvTrxh1 and HvTrxh2 were identified in mature seeds and in seeds after 72 h of germination. Improvement of the established method for identification of thioredoxin-targeted proteins based on two-dimensional electrophoresis and fluorescence labelling of thiol groups was achieved by application of a highly sensitive Cy5 maleimide dye and large-format two-dimensional gels, resulting in a 10-fold increase in the observed number of labelled protein spots. The technique also provided information about accessible thiol groups in the proteins identified in the barley seed proteome. In total, 16 different putative target proteins were identified from 26 spots using tryptic in-gel digestion, matrix-assisted laser-desorption ionization-time-of-flight MS and database search. HvTrxh1 and HvTrxh2 were shown to have similar target specificity. Barley alpha-amylase/subtilisin inhibitor, previously demonstrated to be reduced by both HvTrxh1 and HvTrxh2, was among the identified target proteins, confirming the suitability of the method. Several alpha-amylase/trypsin inhibitors, some of which are already known as target proteins of thioredoxin h, and cyclophilin known as a target protein of m-type thioredoxin were also identified. Lipid transfer protein, embryospecific protein, three chitinase isoenzymes, a single-domain glyoxalase-like protein and superoxide dismutase were novel identifications of putative target proteins, suggesting new physiological roles of thioredoxin h in barley seeds.
Bridged Bicyclo Compounds↗
A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).
BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study. RESULTS: There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed. CONCLUSIONS: The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.
Adult↗
The current status of, and challenges in, the development of CCR5 inhibitors as therapeutics for HIV-1 infection.
The discovery of CCR5 as a HIV-1 co-receptor unfolded the cryptic and complicated process of HIV-1 cellular entry and has provided more than a few entry steps as possible modalities for effective viral intervention. The proof-of-principle has already been established for the use of entry inhibitors against HIV-1 and there is a cautious optimism that several CCR5 inhibitors might soon be added to our armamentarium for therapy of HIV-1 infection.
Animals↗
Cost-effectiveness of screening for coronary artery disease in asymptomatic patients with Type 2 diabetes and additional atherogenic risk factors.
OBJECTIVE: Screening for coronary artery disease (CAD) in asymptomatic diabetic patients with two additional atherogenic risk factors has been recommended by the American College of Cardiology/American Diabetes Association, but its cost-effectiveness is yet to be determined. The present study aims to evaluate the cost-effectiveness of screening and determine acceptable strategies. DESIGN: Cost-effectiveness analysis using a Markov model was performed from a societal perspective to measure the clinical benefit and economic consequences of CAD screening in asymptomatic men with diabetes and two additional atherogenic risk factors. We evaluated cohorts of patients stratified by different age groups, and 10 possible combination pairs of atherogenic risks. Incremental cost-effectiveness of no screening, exercise electrocardiography, exercise echocardiography, or exercise single-photon emission-tomography (SPECT) was calculated. Input data were obtained from the published literature. Outcomes were expressed as U.S. dollars per quality-adjusted life-year (QALY). MEASUREMENTS AND MAIN RESULTS: Compared with no screening, incremental cost-effectiveness ratio of exercise electrocardiography was $41,600/QALY in 60-year-old asymptomatic diabetic men with hypertension and smoking, but was weakly dominated by exercise echocardiography. Exercise echocardiography was most cost-effective, with an incremental cost-effectiveness ratio of $40,800/QALY. Exercise SPECT was dominated by other strategies. Sensitivity analyses found that results varied depending on age, combination of additional atherogenic risk factors, and diagnostic test performance. CONCLUSIONS: Incremental cost-effectiveness ratio of CAD screening in asymptomatic patients with diabetes and two or more additional atherogenic risk factors is shown to be acceptable from a societal perspective. Exercise echocardiography was the most cost-effective strategy, followed by exercise electrocardiography.
Aged↗
Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro.
We identified a novel spirodiketopiperazine (SDP) derivative, AK602/ONO4128/GW873140, which specifically blocked the binding of macrophage inflammatory protein 1alpha (MIP-1alpha) to CCR5 with a high affinity (K(d) of approximately 3 nM), potently blocked human immunodeficiency virus type 1 (HIV-1) gp120/CCR5 binding and exerted potent activity against a wide spectrum of laboratory and primary R5 HIV-1 isolates, including multidrug-resistant HIV-1 (HIV-1(MDR)) (50% inhibitory concentration values of 0.1 to 0.6 nM) in vitro. AK602 competitively blocked the binding to CCR5 expressed on Chinese hamster ovary cells of two monoclonal antibodies, 45523, directed against multidomain epitopes of CCR5, and 45531, specific against the C-terminal half of the second extracellular loop (ECL2B) of CCR5. AK602, despite its much greater anti-HIV-1 activity than other previously published CCR5 inhibitors, including TAK-779 and SCH-C, preserved RANTES (regulated on activation normal T-cell expressed and secreted) and MIP-1beta binding to CCR5(+) cells and their functions, including CC-chemokine-induced chemotaxis and CCR5 internalization, while TAK-779 and SCH-C fully blocked the CC-chemokine/CCR5 interactions. Pharmacokinetic studies revealed favorable oral bioavailability in rodents. These data warrant further development of AK602 as a potential therapeutic for HIV-1 infection.
Animals↗
Physicians' attitudes toward anticoagulant therapy in patients with chronic atrial fibrillation.
INTRODUCTION: Although many clinical trials have demonstrated that anticoagulant therapy substantially reduces the risk of ischemic stroke in patients with atrial fibrillation (AF), some physicians are reluctant to use anticoagulants. We investigated attitudes of physicians in Japan toward anticoagulant therapy in chronic AF patients. METHODS: We conducted a survey at the annual meeting of the Japanese Society of General Medicine. We presented subject physicians with 8 vignettes of chronic AF patients and requested that they indicate their most favored choice of therapy from among 6 strategies including warfarin and aspirin. RESULTS: We distributed 209 questionnaires and received 139 replies (67% response rate). For all 8 vignettes presented, only 26% of the respondents preferred to use anticoagulant therapy in AF patients. Longer clinical experiences and responsibility at a teaching hospital were associated with negative attitude toward anticoagulant therapy, while experience of preventive therapy in patients with thromboembolism due to AF and strong influence of clinical trials of anticoagulant prophylaxis on their practice were associated with positive attitude toward the therapy. Among patient characteristics in the vignettes, a risk of thromboembolism was positively associated with preference for anticoagulant therapy, but an advanced age and a risk of bleeding complications were negatively associated with the preference for the therapy. CONCLUSIONS: The physicians in Japan in this survey, especially those with longer clinical experiences or responsibility at a teaching hospital, have a negative attitude toward anticoagulant therapy in chronic AF patients. An advanced age and a risk of bleeding complications of patients are deterrent factors to the use of anticoagulant therapy.
Aged↗
Neuroendoscopic transventricular surgery for suprasellar cystic mass lesions such as cystic craniopharyngioma and Rathke cleft cyst.
Cystic mass lesions in the suprasellar cistern are often associated with neurological deficits, cognitive disorders, and endocrinological impairments. Many surgical approaches are available to treat these mass lesions, but are technically difficult and cannot remove the lesion completely without risking damage to neurological and endocrinological functions due to the proximity to the surrounding structures. Neuroendoscopic transventricular surgery was performed using a ventricular fiberscope for three patients with craniopharyngiomas and two patients with Rathke cleft cysts, with gamma knife radiosurgery for craniopharyngiomas. The endoscopic transventricular approach is safe and minimally invasive for congenital benign suprasellar cystic lesions, especially arachnoid cysts.
Aged↗
Reduction of peptide character of HIV protease inhibitors that exhibit nanomolar potency against multidrug resistant HIV-1 strains.
Novel HIV protease inhibitors containing a hydroxyethylamine dipeptide isostere as a transition state-mimic king structure were synthesized by combining substructures of known HIV protease inhibitors. Among them, TYA5 and TYB5 were proven to be not only potent enzyme inhibitors (K(i) = 0.12 nM and 0.10 nM, respectively) but also strong anti-HIV agents (IC(50) = 9.5 nM and 66 nM, respectively), even against viral strains with multidrug resistance. Furthermore, insertion of an (E)-alkene dipeptide isostere at the P(1)-P(2) position of TYB5 led to development of a purely nonpeptidic protease inhibitor, TYB1 (K(i) = 0.38 nM, IC(50) = 160 nM).
Dipeptides↗
Japan's contribution to clinical research in gastroenterology and hepatology.
BACKGROUND: Although Japan's contributions to several biomedical fields have already been reported, little is known about Japan's contribution to gastroenterology and hepatology. METHODS: Original articles published in 1991 through 2000 in highly reputed journals in the field of gastroenterology and hepatology were retrieved from the MEDLINE database. The number of articles having an affiliation with a Japanese institution was counted in total, and the number for each journal was also counted. Japan's share of articles regarding clinical trials and randomized controlled trials (RCTs) in this field was also determined, along with the trend over the past decade. RESULTS: Japan's share of articles in this field was 10.6%, ranking third in the world, following the United States (35.1%) and the United Kingdom (11.5%). Japan's share of articles went up significantly as a whole (P = 0.01), while the share for RCTs showed no significant change ( P = 0.57) during this period of time. CONCLUSIONS; Japan's contribution to the field of gastroenterology and hepatology is, in general, acceptable compared with that of other counties, but the contribution for RCTs not satisfactory.
Bibliometrics↗
The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis.
BACKGROUND: Cross-sectional studies revealed that cigarette smokers have lower high-density lipoprotein cholesterol (HDL-C) levels and higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) than nonsmokers. But prospective studies on the effects of cigarette smoking cessation on lipid profile have yielded inconclusive results. METHODS: Relevant English articles were retrieved by keyword searches of MEDLINE (1966-October 2000), Cochrane Library (2000, Issue 2), and cited references. Twenty-seven studies met the following inclusion criteria: (1) prospective cohort study including clinical trials, (2) measuring smoking status and lipid profile of HDL-C, TC, LDL-C, and TG, (3) reporting the changes of lipid concentrations in abstinent smokers, and (4) not using adjuvant antihyperlipidemic drugs. RESULTS: Overall Q statistics for net change of HDL-C, TC, LDL-C, and TG showed heterogeneity. Using a random-effects model, HDL-C level increased significantly [0.100 (CI 0.074 to 0.127) mmol/L] after smoking cessation. However, levels of TC [+0.003 (CI -0.042 to 0.048)], LDL-C [-0.064 (CI -0.149 to 0.021)], and TG [+0.028 (CI -0.014 to 0.071)] did not change significantly after smoking cessation. CONCLUSIONS: Cigarette smoking cessation increases serum levels of HDL-C but not of TC, LDL-C, and TG.
Cholesterol↗
IgA1 molecules produced by tonsillar lymphocytes are under-O-glycosylated in IgA nephropathy.
BACKGROUND: Human serum immunoglobulin A1 (IgA1) has a unique mucine-like structure in its hinge region that contains O-glycans and proline-rich peptides. We previously reported the under-O-glycosylation of the hinge in serum IgA1 and deposited IgA1 in glomeruli (glomerular IgA1) in IgA nephropathy. The clinical development and exacerbation of IgA nephropathy frequently are preceded by episodes of upper respiratory tract infections. Therefore, tonsils, which represent the predominant immunocompetent tissue of the upper respiratory tract, may be related to the pathogenesis of IgA nephropathy. In this study, we investigated the O-glycan structure of IgA1 produced by tonsillar lymphocytes (tonsillar IgA1), suspecting that tonsillar IgA1 is one of the origins of glomerular IgA1 in patients with IgA nephropathy. METHODS: Extracted tonsils were obtained from 7 patients with IgA nephropathy and 5 patients with chronic tonsillitis as controls. Tonsillar lymphocytes separated from extracted tonsils were cultured for 7 days, and IgA1 in the culture medium was purified. The varieties of O-glycans in tonsillar IgA1 were determined from the molecular weights measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: A significant increase in the percentage of asialo-agalacto type O-glycans was found in tonsillar IgA1 in 4 of 7 patients with IgA nephropathy (57.1%) compared with controls. Between the IgA nephropathy and control groups, the difference was statistically significant (P = 0.047). CONCLUSION: This study provides precise information about the structure of O-glycans in tonsillar IgA1 in patients with IgA nephropathy. Our results suggest that tonsils produced the underglycosylated IgA1 molecules in patients with IgA nephropathy.
Adolescent↗
Identification, cloning and characterization of two thioredoxin h isoforms, HvTrxh1 and HvTrxh2, from the barley seed proteome.
Two thioredoxin h isoforms, HvTrxh1 and HvTrxh2, were identified in two and one spots, respectively, in a proteome analysis of barley (Hordeum vulgare) seeds based on 2D gel electrophoresis and MS. HvTrxh1 was observed in 2D gel patterns of endosperm, aleurone layer and embryo of mature barley seeds, and HvTrxh2 was present mainly in the embryo. During germination, HvTrxh2 decreased in abundance and HvTrxh1 decreased in the aleurone layer and endosperm but remained at high levels in the embryo. On the basis of MS identification of the two isoforms, expressed sequence tag sequences were identified, and cDNAs encoding HvTrxh1 and HvTrxh2 were cloned by RT-PCR. The sequences were 51% identical, but showed higer similarity to thioredoxin h isoforms from other cereals, e.g. rice Trxh (74% identical with HvTrxh1) and wheat TrxTa (90% identical with HvTrxh2). Recombinant HvTrxh1, HvTrxh2 and TrxTa were produced in Escherichia coli and purified using a three-step procedure. The activity of the purified recombinant thioredoxin h isoforms was demonstrated using insulin and barley alpha-amylase/subtilisin inhibitor as substrates. HvTrxh1 and HvTrxh2 were also efficiently reduced by Arabidopsis thaliana NADP-dependent thioredoxin reductase (NTR). The biochemical properties of HvTrxh2 and TrxTa were similar, whereas HvTrxh1 had higher insulin-reducing activity and was a better substrate for Arabidopsis NTR than HvTrxh2, with a Km of 13 micro m compared with 44 micro m for HvTrxh2. Thus, barley seeds contain two distinct thioredoxin h isoforms which differ in temporal and spatial distribution and kinetic properties, suggesting that they may have different physiological roles.
Amino Acid Sequence↗
A timesaving method to create a fixed puncture route for the buttonhole technique.
BACKGROUND: Up to now, for a successful buttonhole puncture of the vascular access vessel, the fistula should be punctured by the same experienced medical staff for 2-3 months, using sharp needles, until a fixed puncture route is established. METHODS: We developed a timesaving method to create the fixed puncture route for the buttonhole technique. In this method, after the usual haemodialysis (HD), a newly developed thumbtack-shaped polycarbonate peg is thrust toward the access vessel along the same path as the puncture needle that has just been removed. Then, at the beginning of the next HD, the peg is removed and a dull puncture needle is inserted along the track already formed by the peg left in place. These steps are repeated at each HD session for 14 days. Thereafter, the vascular access is achieved at HD sessions by inserting a dull puncture needle through the established puncture route. RESULTS: This buttonhole puncture approach was used in 37 patients for 3 months. While the polycarbonate peg was in place, patients experienced no restrictions in their normal activities of daily living, except during bathing and showering. As for puncture pain, no patient found the pain of the buttonhole technique to be greater than that of the conventional puncture technique. Moreover, no significant bleeding was noted during HD. With this buttonhole puncture approach, only one patient had enough erythema at the puncture site to suggest possible infection. After HD, the time for bleeding to stop was <10 min in 95% of patients. CONCLUSION: This study showed the new timesaving method for creating a buttonhole to be safe and useful.
Catheters, Indwelling↗
Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro.
We designed, synthesized, and identified UIC-94017 (TMC114), a novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitor (PI) containing a 3(R),3a(S),6a(R)-bis-tetrahydrofuranylurethane (bis-THF) and a sulfonamide isostere which is extremely potent against laboratory HIV-1 strains and primary clinical isolates (50% inhibitory concentration [IC(50)], approximately 0.003 micro M; IC(90), approximately 0.009 micro M) with minimal cytotoxicity (50% cytotoxic concentration for CD4(+) MT-2 cells, 74 micro M). UIC-94017 blocked the infectivity and replication of each of HIV-1(NL4-3) variants exposed to and selected for resistance to saquinavir, indinavir, nelfinavir, or ritonavir at concentrations up to 5 micro M (IC(50)s, 0.003 to 0.029 micro M), although it was less active against HIV-1(NL4-3) variants selected for resistance to amprenavir (IC(50), 0.22 micro M). UIC-94017 was also potent against multi-PI-resistant clinical HIV-1 variants isolated from patients who had no response to existing antiviral regimens after having received a variety of antiviral agents. Structural analyses revealed that the close contact of UIC-94017 with the main chains of the protease active-site amino acids (Asp-29 and Asp-30) is important for its potency and wide spectrum of activity against multi-PI-resistant HIV-1 variants. Considering the favorable pharmacokinetics of UIC-94017 when administered with ritonavir, the present data warrant that UIC-94017 be further developed as a potential therapeutic agent for the treatment of primary and multi-PI-resistant HIV-1 infections.
Amino Acid Substitution↗