Medical and Societal information from the Research Community	Number of Articles: 17,750,454 Number of Contributors: 57 Number of Queries: 12,901,669
	Save this page:  Send this page	Login  or Create a Free Account

GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Results(1-25 of 1,580) Sort By: Publication Date Relevance Took: 0.280 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 64 1 2 3 4 > Last >> (1580 articles found) Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. Apr 28, 1995 H Ichinose,T Ohye,Y Matsuda,T Hori,N Blau,A Burlina,B Rouse,R Matalon,K Fujita,T Nagatsu GTP cyclohydrolase I is the first and rate-limiting enzyme for the biosynthesis of tetrahydrobiopterin in mammals. Previously, we reported three species of human GTP cyclohydrolase I cDNA in a human liver cDNA library (Togari, A., Ichinose, H., Matsumoto, S., Fujita, K., and Nagatsu, T. (1992) Bioc... ( view more )hem. Biophys. Res. Commun. 187, 359-365). Furthermore, very recently, we found that the GTP cyclohydrolase I gene is causative for hereditary progressive dystonia with marked diurnal fluctuation, also known as DOPA-responsive dystonia (Ichinose, H., Ohye, T., Takahashi, E., Seki, N., Hori, T., Segawa, M., Nomura, Y., Endo, K., Tanaka, H., Tsuji, S., Fujita, K., and Nagatsu, T. (1994) Nature Genetics 8, 236-242). To clarify the mechanisms that regulate transcription of the GTP cyclohydrolase I gene and to generate multiple species of mRNA, we isolated genomic DNA clones for the human and mouse GTP cyclohydrolase I genes. Structural analysis of the isolated clones revealed that the GTP cyclohydrolase I gene is encoded by a single copy gene and is composed of six exons spanning approximately 30 kilobases. We sequenced all exon/intron boundaries of the human and mouse genes. Structural analysis also demonstrated that the heterogeneity of GTP cyclohydrolase I mRNA is caused by an alternative usage of the splicing acceptor site at the sixth exon. The transcription start site of the mouse GTP cyclohydrolase I gene and the 5'-flanking sequences of the mouse and human genes were determined. We performed regional mapping of the mouse gene by fluorescence in situ hybridization, and the mouse GTP cyclohydrolase I gene was assigned to region C2-3 of mouse chromosome 14. We identified missense mutations in patients with GTP cyclohydrolase I deficiency and expressed mutated enzymes in Escherichia coli to confirm alterations in the enzyme activity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Tissue-specific alternative splicing of the first exon generates two types of mRNAs in human aromatic L-amino acid decarboxylase. Nov 24, 1992 H Ichinose,C Sumi-Ichinose,T Ohye,Y Hagino,K Fujita,T Nagatsu Aromatic-L-amino-acid decarboxylase (AADC) is an enzyme that plays an essential role in synthesizing catecholamines and serotonin in neuronal and endocrine tissues. AADC has also been detected in other nonneuronal tissues including liver and kidney, although its physiological role in nonneuronal ti... ( view more )ssues has not yet been defined. Previously we have cloned a human AADC cDNA from a neuronal tissue (pheochromocytoma) [Ichinose, H., Kurosawa, Y., Titani, K., Fujita, K., & Nagatsu, T. (1989) Biochem. Biophys. Res. Commun. 164, 1024-1030] and the corresponding genomic DNA [Sumi-Ichinose, C., Ichinose, H., Takahashi, E., Hori, T., & Nagatsu, T. (1992) Biochemistry 31, 2229-2238]. Here we present isolation and characterization of AADC cDNA and genomic DNA from a nonneuronal tissue (human liver). The nonneuronal and neuronal AADC mRNAs differed only in the region corresponding to the untranslated first exon. The first exon for the nonneuronal-type mRNA was located 4.2 kilobases upstream to that for the neuronal-type mRNA and 22 kilobases from exon 2, to which it is spliced. Determination of the transcription initiation site indicated that the length of the nonneuronal-type exon 1 was 200 bp. A TATA box-like motif was located between positions -26 and -20 from the transcription initiation site. These results showed that an alternative usage of the first exon in the 5'-untranslated regions produces two types of mRNAs in AADC and suggested that alternative splicing would regulate the tissue-specific expression of AADC. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Spontaneous baroreflex control of cardiac output during dynamic exercise, muscle metaboreflex activation, and heart failure. Mar 2008 Masashi Ichinose,Javier A Sala-Mercado,Donal S O'Leary,Robert L Hammond,Matthew Coutsos,Tomoko Ichinose,Marco Pallante,Ferdinando Iellamo We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaborefl... ( view more )ex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (-3.08 +/- 0.5 vs. -5.14 +/- 0.6 beats.min(-1).mmHg(-1); P < 0.05) and CO-LVSP (-134.74 +/- 24.5 vs. -208.6 +/- 22.2 ml.min(-1).mmHg(-1); P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 +/- 2.8% vs. 52.3 +/- 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Spontaneous baroreflex control of heart rate versus cardiac output: altered coupling in heart failure. Mar 2008 Javier A Sala-Mercado,Masashi Ichinose,Robert L Hammond,Matthew Coutsos,Tomoko Ichinose,Marco Pallante,Ferdinando Iellamo,Donal S O'Leary Dynamic cardiac baroreflex responses are frequently investigated by analyzing the spontaneous reciprocal changes in arterial pressure and heart rate (HR). However, whether the spontaneous baroreflex-induced changes in HR translate into changes in cardiac output (CO) is unknown. In addition, this li... ( view more )nkage between changes in HR and changes in CO may be different in subjects with heart failure (HF). We examined these questions using conscious dogs before and after pacing-induced HF. Spontaneous baroreflex sensitivity in the control of HR and CO was evaluated as the slopes of the linear relationships between HR or CO and left ventricular systolic pressure (LVSP) during spontaneous sequences of greater or equal to three consecutive beats when HR or CO changed inversely versus pressure. Furthermore, the translation of baroreflex HR responses into CO responses (HR-CO translation) was examined by computing the overlap between HR and CO sequences. In normal resting conditions, 44.0 +/- 4.4% of HR sequences overlapped with CO sequences, suggesting that only around half of the baroreflex HR responses cause CO responses. In HF, HR-LVSP, CO-LVSP, and the HR-CO translation significantly decreased compared with the normal condition (-2.29 +/- 0.5 vs. -5.78 +/- 0.7 beats.min(-1).mmHg(-1); -70.95 +/- 11.8 vs. -229.89 +/- 29.6 ml.min(-1).mmHg(-1); and 19.66 +/- 4.9 vs. 44.0 +/- 4.4%, respectively). We conclude that spontaneous baroreflex HR responses do not always cause changes in CO. In addition, HF significantly decreases HR-LVSP, CO-LVSP, and HR-CO translation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Spontaneous baroreflex control of heart rate during exercise and muscle metaboreflex activation in heart failure. Sep 2007 Ferdinando Iellamo,Javier A Sala-Mercado,Masashi Ichinose,Robert L Hammond,Marco Pallante,Tomoko Ichinose,Larry W Stephenson,Donal S O'Leary In heart failure (HF), there is a reduced baroreflex sensitivity at rest, and during dynamic exercise there is enhanced muscle metaboreflex activation (MRA). However, how the arterial baroreflex modulates HR during exercise is unknown. We tested the hypothesis that spontaneous baroreflex sensitivit... ( view more )y (SBRS) is attenuated during exercise in HF and that MRA further depresses SBRS. In seven conscious dogs we measured heart rate (HR), cardiac output, and left ventricular systolic pressure at rest and during mild and moderate dynamic exercise, before and during MRA (via imposed reductions of hindlimb blood flow), and before and after induction of HF (by rapid ventricular pacing). SBRS was assessed by the sequences method. In control, SBRS was reduced from rest with a progressive resetting of the baroreflex stimulus-response relationship in proportion to exercise intensity and magnitude of MRA. In HF, SBRS was significantly depressed in all settings; however, the changes with exercise and MRA occurred with a pattern similar to the control state. As in control, the baroreflex stimulus-response relationship showed an intensity- and muscle metaboreflex (MMR)-dependent rightward and upward shift. The results of this study indicate that HF induces an impairment in baroreflex control of HR at rest and during exercise, although the effects of exercise and MRA on SBRS occur with a similar pattern as in control, indicating the persistence of some vagal activity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise. Jun 2007 Javier A Sala-Mercado,Masashi Ichinose,Robert L Hammond,Tomoko Ichinose,Marco Pallante,Larry W Stephenson,Donal S O'Leary,Ferdinando Iellamo Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine ... ( view more )whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Microtia: a new chronology for the total external ear reconstruction. A retrospective study of eight cases] Oct 2000 A Danino,S Yoshimoto,M Ichinose,T Kuroki,J M Servant After 14 months of personal training with Professor Ichinose's team in Chiba (Japan), the author reports a new chronology of the total external ear reconstruction for microtia. This approach, proposed by Dr Yoshimoto, subtracts in time spent on creating the cartilaginous framework from the total ge... ( view more )neral anesthesia time. The principles of this technique and its chronology are described. The results of eight patients operated according to this method between February 1994 and October 1999 are analyzed and compared to the 35 previous reconstructions performed by this team. The advantage of this chronology has been established: this method allows a considerable reduction of the general anesthesia time, a rationalization of the cost of these reconstructions, an increased comfort for the patients and an easier learning process for young plastic surgeons. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Molecular biology of hereditary dystonia] Mar 1998 T Nagatsu,H Ichinose The causative genes of hereditary dystonia (hereditary progressive dystonia, HPD; dopa-responsive dystonia, DRD) were discovered in 1994-1995. HPD/DRD is caused by the deficiency of dopamine to less than 20% of the normal level in the nigro-striatum of the brain owing to the mutations of the dopami... ( view more )ne synthesizing enzymes. Autosomal dominant dystonia (Segawa's disease) was found to be caused by mutations of GTP cyclohydrolase I which synthesizes tetrahydrobiopterin, the cofactor of tyrosine hydroxylase, by Ichinose et al. (Nature Genetics, 1994) in Japan. Autosomal recessive dystonia was reported to be caused by mutations of tyrosine hydroxylase by Lüdecke et al. (Human Genetics, 1995) in Germany. Hereditary dystonia, especially autosomal dominant Segawa's disease can be completely controlled by L-dopa administration. Measurement of the activity of GTP cyclohydrolase I in mononuclear blood cells is useful for the diagnosis of Segawa's disease. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Stage-specific elevated expression of the genes for hepatocyte growth factor, keratinocyte growth factor, and their receptors during the morphogenesis and differentiation of rat stomach mucosa. May 24, 1996 Y Matsubara,M Ichinose,M Tatematsu,M Ichinose,M Oka,N Yahagi,K Kurokawa,T Kageyama,K Miki,H Fukamachi Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are two factors considered to be involved in the morphogenesis of several organs. To understand the role of HGF and KGF in the stomach development, we analyzed changes in the levels of expression of the genes for the two growth fac... ( view more )tors and their receptors in the fetal rat stomach by competitive RT-PCR. Resembling our previous results for HGF, the expression of the genes for KGF and its receptor was observed in the mesenchyme and epithelium of 16.5 day fetal stomach, respectively, indicating the possibility that KGF mediates the epithelial-mesenchymal interaction in the early stage of stomach development. The developmental profile of the expression of the genes for the two growth factors and their receptors were different, indicating a difference in their roles; the genes for HGF and c-met, the receptor for HGF, are expressed mainly during the morphogenetic period, while the genes for KGF and its receptor mainly after the morphogenetic period. Thus, it is probable that HGF controls the proliferation of epithelial cells during the morphogenetic process. The expression of the genes for KGF and its receptor is not correlated with epithelial proliferation during morphogenesis, but it does appear to be linked with epithelial differentiation. These results, together with the absence of significant mitogenic effect of KGF on the epithelial cells of the fetal rat glandular stomach in vitro, suggest a role for KGF as a differentiation factor. In addition, the expression profile of the genes for KGF and its receptor towards the end of fetal period appears to be closely correlated with that of mesenchymal cell proliferation, suggesting another role for the growth factor that is not regulated by the epithelial-mesenchymal interaction. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Limulus hemocyte transglutaminase. cDNA cloning, amino acid sequence, and tissue localization. Jan 5, 1993 F Tokunaga,T Muta,S Iwanaga,A Ichinose,E W Davie,K Kuma,T Miyata We have evidence that the limulus (Tachypleus tri-dentatus) hemocyte transglutaminase (TGase) has a molecular mass of 86 kDa and properties of the mammalian type II TGase-like enzyme (Tokunaga, F., Yamada, M., Miyata, T., Ding, Y.-L., Hiranaga-Kawabata, M., Muta, T., Iwanaga, S., Ichinose, A., and ... ( view more )Davie, E.W. (1993) J. Biol. Chem. 268, 252-261). We present here the cDNA and amino acid sequences, and localization of the TGase in various tissues of limulus. The cloned cDNA for TGase consists of 2,884 base pairs. An open reading frame of 2,292 base pairs encodes a sequence comprising 764 residues of the mature protein with molecular masses of 87,021 and 87,110 Da, due to two different clones. The discrepancies of nucleotides in these two clones result in 3 amino acid exchanges at positions Gly452(GGT)-Arg(CGT), Ser477(AGT)-Cys(TGT), and Ile486(ATC)-Ser(AGC), respectively. Northern blot analysis on a total RNA extracted from various tissues of limulus revealed that TGase is expressed with 3.0 kilobases of a single type of mRNA, mainly in hemocytes, hepatopancreas, and gastric tissues. Limulus TGase shows significant sequence similarity with the mammalian TGase family, as follows: guinea pig liver TGase (32.7%), human factor XIIIa subunit (34.7%), human keratinocyte TGase (37.6%), and human erythrocyte band 4.2 (23.0%). Limulus TGase has a unique NH2-terminal cationic extension of 60 residues with no homology to the NH2 termini of mammalian TGases. Based on the alignment of the amino acid sequence of limulus TGase with those of the known TGase family, a phylogenetic tree representing an evolutionary relationship among the family members was inferred by the neighbor joining method. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Identification and characterization of gyrB mutants of Escherichia coli that are defective in partitioning of mini-F plasmids. Mar 1990 T Ogura,H Niki,H Mori,M Morita,M Hasegawa,C Ichinose,S Hiraga hopA mutants, which have been suggested to be defective in mini-F plasmid partitioning (H. Niki, C. Ichinose, T. Ogura, H. Mori, M. Morita, M. Hasegawa, N. Kusukawa, and S. Hiraga, J. Bacteriol. 170:5272-5278, 1988), were found to carry mutations in the gyrB gene, coding for the B subunit of DNA gy... ( view more )rase. In gyrB(HopA) mutants, relaxation of the superhelicity of plasmids, increased IncG incompatibility, and increased SopB protein production were observed. It is suggested that altered expression of the sop genes, which is due to relaxation of the mini-F plasmid DNA, causes both defective partitioning of the mini-F plasmids and increased IncG incompatibility in gyrB(HopA) mutants. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Risk of gastric cancer in asymptomatic, middle-aged Japanese subjects based on serum pepsinogen and Helicobacter pylori antibody levels. Aug 15, 2008 Kimihiko Yanaoka,Masashi Oka,Noriko Yoshimura,Chizu Mukoubayashi,Shotaro Enomoto,Mikitaka Iguchi,Hirohito Magari,Hirotoshi Utsunomiya,Hideyuki Tamai,Kenji Arii,Nobutake Yamamichi,Mitsuhiro Fujishiro,Tatsuya Takeshita,Osamu Mohara,Masao Ichinose A total of 5,209 asymptomatic, middle-aged subjects, whose serum pepsinogen (PG) and Helicobacter pylori antibody levels had been assessed, were followed for 10 years. Subjects with positive serum H. pylori antibodies (>50 U/mL) had an increased cancer risk (HR = 3.48, 95% CI = 1.26-9.64). Risk of ... ( view more )gastric cancer increased as the antibody level increased; the H. pylori-positive group with antibody levels >500 U/mL had the highest incidence rate (325/100,000 person-years). Cancer development also increased with a reduced serum PG I level or a reduced PG I/II ratio; the risk was significantly elevated with serum PG I level or=30 ng/mL (HR = 3.81, 95% CI = 1.10-13.21). Using H. pylori antibody and PG levels, subgroups with an especially high or low cancer incidence rate could be identified. H. pylori-negative or indeterminate subjects with low PG level (PG I 500 U/mL and a low PG level were among the subgroups with a high cancer incidence rate (over 400/100,000 person-years). In contrast, H. pylori-negative subjects with a PG I level >70 ng/mL or a PG I/II ratio >3.0 had the lowest risk; none of these subjects developed cancer. Thus, serum PG levels and/or H. pylori antibody levels can be used to predict the risk of cancer in individuals with H. pylori-related gastritis from the general population. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Gender-specific hypertension and responsiveness to nitric oxide in sGC{alpha}1 knockout mice. Jul 1, 2008 Emmanuel S Buys,Patrick Sips,Pieter Vermeersch,Michael J Raher,Elke Rogge,Fumito Ichinose,Mieke Dewerchin,Kenneth D Bloch,Stefan Janssens,Peter Brouckaert AIM: The effects of nitric oxide (NO) in the cardiovascular system are attributed in part to cGMP synthesis by the alpha(1)beta(1) isoform of soluble guanylate cyclase (sGC). Because available sGC inhibitors are neither enzyme- nor isoform-specific, we generated knockout mice for the alpha(1) subun... ( view more )it (sGCalpha(1)(-/-) mice) in order to investigate the function of sGCalpha(1)beta(1) in the regulation of blood pressure and cardiac function. METHODS AND RESULTS: Blood pressure was evaluated, using both non-invasive and invasive haemodynamic techniques, in intact and gonadectomized male and female sGCalpha(1)(-/-) and wild-type (WT) mice. Cardiac function was assessed with a conductance catheter inserted in the left ventricle of male and female sGCalpha(1)(-/-) and WT mice. Male sGCalpha(1)(-/-) mice developed hypertension (147 +/- 2 mmHg), whereas female sGCalpha(1)(-/-) mice did not (115 +/- 2 mmHg). Orchidectomy and treatment with an androgen receptor antagonist prevented hypertension, while ovariectomy did not influence the phenotype. Chronic testosterone treatment increased blood pressure in ovariectomized sGCalpha(1)(-/-) mice but not in WT mice. The NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride raised blood pressure similarly in male and female WT and sGCalpha(1)(-/-) mice. The ability of NO donor compounds to reduce blood pressure was slightly attenuated in sGCalpha(1)(-/-) male and female mice as compared to WT mice. The direct sGC stimulator BAY 41-2272 reduced blood pressure only in WT mice. Increased cardiac contractility and arterial elastance as well as impaired ventricular relaxation were observed in both male and female sGCalpha(1)(-/-) mice. CONCLUSION: These findings demonstrate that sGCalpha(1)beta(1)-derived cGMP signalling has gender-specific and testosterone-dependent cardiovascular effects and reveal that the effects of NO on systemic blood pressure do not require sGCalpha(1)beta(1). ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Interstitial lung disease in Japanese patients with lung cancer: a cohort and nested case-control study. Jun 15, 2008 Shoji Kudoh,Harubumi Kato,Yutaka Nishiwaki,Masahiro Fukuoka,Kouichiro Nakata,Yukito Ichinose,Masahiro Tsuboi,Soichiro Yokota,Kazuhiko Nakagawa,Moritaka Suga,Japan Thoracic Radiology Group ,Haiyi Jiang,Yohji Itoh,Alison Armour,Claire Watkins,Tim Higenbottam,Fredrik Nyberg RATIONALE: Interstitial lung disease (ILD) occurs in Japanese patients with non-small cell lung cancer (NSCLC) receiving gefitinib. OBJECTIVES: To elucidate risk factors for ILD in Japanese patients with NSCLC during treatment with gefitinib or chemotherapy. METHODS: In a prospective epidemiologic ... ( view more )cohort, 3,166 Japanese patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551). Patients who developed acute ILD (n = 122) and randomly selected control subjects (n = 574) entered a case-control study. Adjusted incidence rate ratios were estimated from case-control data by odds ratios (ORs) with 95% confidence intervals (CIs) using logistic regression. Crude (observed) incidence rates and risks were calculated from cohort data. MEASUREMENTS AND MAIN RESULTS: The observed (unadjusted) incidence rate over 12 weeks was 2.8 (95% CI, 2.3-3.3) per 1,000 person-weeks, 4.5 (3.5-5.4) for gefitinib versus 1.7 (1.2-2.2) for chemotherapy; the corresponding observed naive cumulative incidence rates at the end of 12-week follow-up were 4.0% (3.0-5.1%) and 2.1% (1.5-2.9%), respectively. Adjusted for imbalances in risk factors between treatments, the overall OR for gefitinib versus chemotherapy was 3.2 (1.9-5.4), elevated chiefly during the first 4 weeks (3.8 [1.9-7.7]). Other ILD risk factors in both groups included the following: older age, poor World Health Organization performance status, smoking, recent NSCLC diagnosis, reduced normal lung on computed tomography scan, preexisting chronic ILD, concurrent cardiac disease. ILD-related deaths in patients with ILD were 31.6% (gefitinib) versus 27.9% (chemotherapy); adjusted OR, 1.05 (95% CI, 0.3-3.2). CONCLUSIONS: ILD was relatively common in these Japanese patients with NSCLC during therapy with gefitinib or chemotherapy, being higher in the older, smoking patient with preexisting ILD or poor performance status. The risk of developing ILD was higher with gefitinib than chemotherapy, mainly in the first 4 weeks. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Enhanced nerve regeneration through a bilayered chitosan tube: the effect of introduction of glycine spacer into the CYIGSR sequence. Jun 15, 2008 Wei Wang,Soichiro Itoh,Atsushi Matsuda,Tomoyasu Aizawa,Makoto Demura,Shizuko Ichinose,Kenichi Shinomiya,Junzo Tanaka We have developed a novel bilayered chitosan tube that comprises an outer layer of chitosan film and an inner layer of chitosan nonwoven nano/microfiber mesh. The tube is fabricated with an electrospinning method. We characterized the microstructure and mechanical properties of this material. We in... ( view more )troduced glycine spacers into the CYIGSR sequence, domain of laminin-1 that enhances Schwann cells migration and attachment, as well as neural outgrowth, resulting in the amino acid sequences CGGYIGSR and CGGGGGGYIGSR. These peptides were covalently bound to the nano/microfiber mesh surface of the chitosan tube to examine the effects of peptide mobility on nerve regeneration. Scaffolds constructed from these bilayered chitosan tubes were grafted to bridge injured sciatic nerve. Isografting was performed as a control. These scaffolds were removed 5 and 10 weeks after implantation for histological analysis. Nerve regeneration into chitosan tubes, on which the CGGGGGGYIGSR peptide was immobilized, exhibited efficacy similar to that of the isograft and represent a promising candidate for promoting peripheral nerve repair. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Enzymatic Characteristics of I213T Mutant Presenilin-1/{gamma}-Secretase in Cell Models and Knock-in Mouse Brains: FAMILIAL ALZHEIMER DISEASE-LINKED MUTATION IMPAIRS {gamma}-SITE CLEAVAGE OF AMYLOID PRECURSOR PROTEIN C-TERMINAL FRAGMENT {beta}. Jun 13, 2008 Masafumi Shimojo,Naruhiko Sahara,Tatsuya Mizoroki,Satoru Funamoto,Maho Morishima-Kawashima,Takashi Kudo,Masatoshi Takeda,Yasuo Ihara,Hiroshi Ichinose,Akihiko Takashima Presenilin (PS)/gamma-secretase-mediated intramembranous proteolysis of amyloid precursor protein produces amyloid beta (Abeta) peptides in which Abeta species of different lengths are generated through multiple cleavages at the gamma-, zeta-, and epsilon-sites. An increased Abeta42/Abeta40 ratio i... ( view more )s a common characteristic of most cases of familial Alzheimer disease (FAD)-linked PS mutations. However, the molecular mechanisms underlying amyloid precursor protein proteolysis leading to increased Abeta42/Abeta40 ratios still remain unclear. Here, we report our findings on the enzymatic analysis of gamma-secretase derived from I213T mutant PS1-expressing PS1/PS2-deficient (PS(-/-)) cells and from the brains of I213T mutant PS1 knock-in mice. Kinetics analyses revealed that the FAD mutation reduced de novo Abeta generation, suggesting that mutation impairs the total catalytic rate of gamma-secretase. Analysis of each Abeta species revealed that the FAD mutation specifically reduced Abeta40 levels more drastically than Abeta42 levels, leading to an increased Abeta42/Abeta40 ratio. By contrast, the FAD mutation increased the generation of longer Abeta species such as Abeta43, Abeta45, and >Abeta46. These results were confirmed by analyses of gamma-secretase derived from I213T knock-in mouse brains, in which the reduction of de novo Abeta generation was mutant allele dose-dependent. Our findings clearly indicate that the mechanism underlying the increased Abeta42/Abeta40 ratio observed in cases of FAD mutations is related to the differential inhibition of gamma-site cleavage reactions, in which the reaction producing Abeta40 is subject to more inhibition than that producing Abeta42. Our results also provide novel insight into how enhancing the generation of longer Abetas may contribute to Alzheimer disease onset. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Changes in blood flow in conduit artery and veins of the upper arm during leg exercise in humans. Jun 2008 Anna Ooue,Tomoko K Ichinose,Yoshimitsu Inoue,Takeshi Nishiyasu,Shunsaku Koga,Narihiko Kondo This study investigated changes in blood flow in the conduit artery, superficial vein, and deep vein of the upper arm during increase in internal temperature due to leg cycling. Additionally, we sought to demonstrate the contributions of blood velocity and vessel diameter on blood flow responses. F... ( view more )ourteen subjects performed supine cycling exercise at 60-69% maximal oxygen uptake for 30 min at an ambient temperature of 28 degrees C and relative humidity of 50%. Blood velocity and diameter in the brachial artery, basilic vein (superficial vein), and brachial vein (deep vein) were measured using ultrasound Doppler, and blood flow was calculated. Blood flow in the artery and superficial vein increased linearly with rising oesophageal temperature (DeltaT (oes)) after DeltaT (oes) was about 0.3 degrees C (within threshold), as well as cutaneous vascular conductance on the forearm. Changes in blood velocity in these vessels were similar to those in blood flow. Conversely, the brachial artery and superficial vein diameter did not affect the blood flow response. Blood flow variables in the deep vein did not change remarkably with rising DeltaT (oes). These results suggest that blood flow response, by an increase in velocity, in the conduit artery with rising DeltaT (oes) during exercise is similar to that in the superficial vein, but not deep vein. Also, it is indicated that these increases in blood flow relate to the increase in skin blood flow on the forearm with the rise in body temperature during exercise. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Antiviral activities of coffee extracts in vitro. Jun 2008 Hirotoshi Utsunomiya,Masao Ichinose,Misao Uozaki,Kazuko Tsujimoto,Hisashi Yamasaki,A Hajime Koyama Both hot water extracts of coffee grinds and instant coffee solutions inhibited the multiplication of herpes simplex virus type 1, a representative enveloped DNA virus, when they were added to the culture medium of the virus-infected cells at a dose of one fifth the concentration suitable for drink... ( view more )ing. The antiherpetic activity was independent of the suppliers (companies) of the coffee grinds and of the locations where the coffee beans were produced. Further characterization revealed that there are two different mechanisms, by which the coffee extracts exert inhibitory activities on the virus infection; (1) a direct inactivation of the infectivity of virus particle (i.e., a virucidal activity) and (2) the inhibition of progeny infectious virus formation at the late stage of viral multiplication in the infected cells. Caffeine, but not quinic acid and chlorogenic acid, inhibited the virus multiplication to some extent, but none of them showed the virucidal activity, suggesting that other component(s) in the coffee extracts must play a role in the observed antiviral activity. In addition, the coffee extracts inhibited the multiplication of poliovirus, a non-enveloped RNA virus, but showed no virucidal effect on this virus. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Tegafur-uracil plus gemcitabine combination chemotherapy in patients with advanced non-small cell lung cancer previously treated with platinum. Jun 2008 Takashi Seto,Takeharu Yamanaka,Makiko Nakano,Mayuko Ota,Riichiroh Maruyama,Tatsuro Okamoto,Hiroshi Wataya,Kazutsugu Uematsu,Nobuhiko Seki,Kenji Eguchi,Hiroshi Semba,Yukito Ichinose BACKGROUND: An open-label, single-arm prospective study was conducted to evaluate the efficacy and toxicity of the combination of gemcitabine and tegafur-uracil (UFT) in patients with advanced nonsmall-cell lung cancer (NSCLC) after the failure of previous platinum-containing regimens. PATIENTS AND... ( view more ) METHODS: Patients with advanced NSCLC received 200 mg/m2 of UFT twice daily from day 1 through 14 plus 900 mg/m2 of gemcitabine per day via intravenous injection on days 8 and 15. This regimen was repeated every 3 or 4 weeks. RESULTS: A total of 40 patients were enrolled. Eleven patients (28%; 95% confidence interval [CI], 15-44%) achieved a partial response. The median progression-free survival, median overall survival, and 1-year survival rate were 4.0 months (95% CI, 3.3-6.7 months), 12.6 months (95% CI, 7.0-22.3 months), and 51% (95% CI, 33-66%), respectively. The most common grade 3 or 4 toxicity was neutropenia (38%; 95% CI, 23-54%) and the rate of grade 3 or 4 nonhematologic toxicity remained at less than 5%. A multivariate Cox model showed that adenocarcinoma, nonsmoking history, and good performance status predicted better survival. CONCLUSIONS: Combination chemotherapy with UFT and gemcitabine showed a promising effectiveness and acceptable toxicity for patients with platinum-resistant NSCLC. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Protective effects of ebselen, a seleno-organic antioxidant on neurodegeneration induced by hypoxia and reperfusion in stroke-prone spontaneously hypertensive rat. May 2, 2008 K Yamagata,S Ichinose,A Miyashita,M Tagami Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippocampal neurons in the stroke-prone spontaneously hypertensive rat (SHRSP) but not in Wistar Kyoto rats (WKY). We investigated whether 2-phenyl-1,2-benzisoselenazol-3(2H)-one, also called PZ51 (ebselen), useful for treating i... ( view more )schemic damage or antihypertension in the brain, can protect against ischemic neuronal damage in SHRSP. In this study, we compared the effects of ebselen, carvedilol, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) as well as vitamin E, added to cultures of neurons after reoxygenation (20% O(2)) following hypoxia (1% O(2)). SHRSP neurons died rapidly during reoxygenation following hypoxia but were rescued in large measure by 10 muM ebselen (neuronal death; 2.7+/-1.4%). In order of neuroprotective potency, the agents ranked as follows: ebselen>carvedilol>MCI-186>vitamin E. In vivo, strong neuroprotection by ebselen was observed in the hippocampal CA1 region of SHRSP (32.9+/-9.5 apoptotic neuron/1000 neurons, 30 mg/kg/day). Ebselen prevented apoptosis as confirmed by morphological observations in vivo. Its effect was associated with the expression of Bcl-2 and Bax. These findings suggest that ebselen has a marked inhibitory effect on neuronal damage during stroke. Ebselen may be effective in the prevention and/or treatment of neurodegenerative diseases associated with excessive apoptosis in patients with stroke. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis. May 2, 2008 Yutaka Kawahito,Sizuko Ichinose,Hajime Sano,Yasunori Tsubouchi,Masataka Kohno,Toshikazu Yoshikawa,Daisaku Tokunaga,Tatsuya Hojo,Ryo Harasawa,Teruaki Nakano,Kazuhiro Matsuda Mycoplasma fermentans has been suspected as one of the causative pathogenic microorganisms of rheumatoid arthritis (RA) however, the pathogenic mechanism is still unclear. We, previously, reported that glycolipid-antigens (GGPL-I and III) are the major antigens of M. fermentans. Monoclonal antibody... ( view more ) against the GGPL-III could detect the existence of the GGPL-III antigens in synovial tissues from RA patients. GGPL-III antigens were detected in 38.1% (32/84) of RA patient's tissues, but not in osteoarthritis (OA) and normal synovial tissues. Immunoelectron microscopy revealed that a part of GGPL-III antigens are located at endoplasmic reticulum. GGPL-III significantly induced TNF-alpha and IL-6 production from peripheral blood mononulear cells, and also proliferation of synovial fibroblasts. Further study is necessary to prove that M. fermentans is a causative microorganism of RA; however, the new mechanisms of disease pathogenesis provides hope for the development of effective and safe immunotherapeutic strategies based on the lipid-antigen, GGPL-III, in the near future. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. May 2008 J S Palumbo,K A Barney,E A Blevins,M A Shaw,A Mishra,M J Flick,K W Kombrinck,K E Talmage,M Souri,A Ichinose,J L Degen BACKGROUND: Multiple studies suggest that the hemostatic and innate immune systems functionally cooperate in establishing the fraction of tumor cells that successfully form metastases. In particular, platelets and fibrinogen have been shown to support metastatic potential through a mechanism couple... ( view more )d to natural killer (NK) cell function. As the transglutaminase that ultimately stabilizes platelet/fibrin thrombi through the covalent crosslinking of fibrin, factor (F) XIII is another thrombin substrate that is likely to support hematogenous metastasis. OBJECTIVE: Directly define the role of FXIII in tumor growth, tumor stroma formation, and metastasis. METHODS: Tumor growth and metastatic potential were quantitatively and qualitatively evaluated in wild-type mice and gene-targeted mice lacking the catalytic FXIII-A subunit. RESULTS: Loss of FXIIIa function significantly diminished hematogenous metastatic potential in both experimental and spontaneous metastasis assays in immunocompetent mice. However, FXIII was not required for the growth of established tumors or tumor stroma formation. Rather, detailed analyses of the early fate of circulating tumor cells revealed that FXIII supports the early survival of micrometastases by a mechanism linked to NK cell function. CONCLUSIONS: Factor XIII is a significant determinant of metastatic potential and supports metastasis by impeding NK cell-mediated clearance of tumor cells. Given that these findings parallel previous observations in fibrinogen-deficient mice, an attractive hypothesis is that FXIII-mediated stabilization of fibrin/platelet thrombi associated with newly formed micrometastases increases the fraction of tumor cells capable of evading NK cell-mediated lysis. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effects of asian sand dust, Arizona sand dust, amorphous silica and aluminum oxide on allergic inflammation in the murine lung. May 2008 Takamich Ichinose,Seiichi Yoshida,Kaori Sadakane,Hrohisa Takano,Rie Yanagisawa,Kenichi Inoue,Masataka Nishikawa,Ikuko Mori,Hiroaki Kawazato,Aiko Yasuda,Takayuki Shibamoto The aggravating effects of Asian sand dust (SD) and related minerals on the allergic inflammation were examined in the murine lungs. The toxic materials adsorbed onto Asian SD, Arizona SD were inactivated by heat-treatment. ICR mice were administered mineral samples (0.1 mg/mouse) and/or ovalbumin ... ( view more )(OVA) (1 microg/mouse) - normal saline (control), Asian SD, Arizona SD, SiO2, Al2O3, OVA, OVA + Asian SD, OVA + Arizona SD, OVA + SiO2, and OVA + Al2O3 - intratracheally four times at two-week intervals. All samples tested enhanced eosinophil recruitment induced by ovalbumin in the submucosa of the airway, which has a goblet cell proliferation in the bronchial epithelium. Arizona SD alone caused a slight increase of neutrophils in bronchoalveolar lavage fluids along with pro-inflammatory mediators, such as keratinocyte chemoattractant, but Asian SD alone or Al2O3 alone showed no effect. The test particles, except Al2O3, synergistically increased the numbers of eosinophils in BALF induced by ovalbumin. In particular, Arizona SD and SiO2 synergistically increased the eosinophil relevant cytokine and chemokine, such as IL-5 and monocyte chemotactic protein (MCP)-3. The aggravating effects of the samples were dependent on the SiO2 content. All samples tested also induced the adjuvant effects to specific IgG1 production by OVA. These results suggest that the aggravated allergic inflammation by mineral dusts may be due to the mineral elements (mainly SiO2). The enhancement by Arizona SD may be mediated, at least partially, by the increased expression of IL-5 and MCP-3 and also by the modulated expression of IL-5 and MCP-3. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Impaired meningeal development in association with apical expansion of calvarial bone osteogenesis in the Foxc1 mutant. May 2008 Philaiporn Vivatbutsiri,Shizuko Ichinose,Marjo Hytönen,Kirsi Sainio,Kazuhiro Eto,Sachiko Iseki Loss of function of the mouse forkhead/winged helix transcription factor Foxc1 induces congenital hydrocephalus and impaired skull bone development due to failure of apical expansion of the bone. In this study we investigated meningeal development in the congenital hydrocephalus (ch) mouse with spo... ( view more )ntaneous loss of function mutant of Foxc1, around the period of initiation of skull bone apical expansion. In situ hybridization of Runx2 revealed active apical expansion of the frontal bone begins between embryonic day 13.5 and embryonic day 14.5 in the wild type, whereas expansion was inhibited in the mutant. Ultrastructural analysis revealed that three layers of the meninges begin to develop at E13.5 in the basolateral site of the head and subsequently progress to the apex in wild type. In ch homozygotes, although three layers were recognized at first at the basolateral site, cell morphology and structure of the layers became abnormal except for the pia mater, and arachnoidal and dural cells never differentiated in the apex. We identified meningeal markers for each layer and found that their expression was down-regulated in the mutant arachnoid and dura maters. These results suggest that there is a close association between meningeal development and the apical growth of the skull bones. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Efficacy and safety of pemetrexed in combination with cisplatin for malignant pleural mesothelioma: a phase I/II study in Japanese patients. May 2008 Kazuhiko Nakagawa,Koichi Yamazaki,Hideo Kunitoh,Toyoaki Hida,Kenichi Gemba,Tetsu Shinkai,Yukito Ichinose,Susumu Adachi,Yoshihiro Nambu,Nagahiro Saijo,Masahiro Fukuoka BACKGROUND: Pemetrexed in combination with cisplatin (Pem/Cis) is used globally for the treatment of malignant pleural mesothelioma (MPM). This Phase I/II study was conducted to determine the recommended dose (RD) (Phase I) of Pem/Cis, and evaluate the efficacy and safety (Phase II) in Japanese MPM... ( view more ) patients. METHODS: Key eligibility criteria were histologic diagnosis of MPM incurable by surgery, no prior chemotherapy, and a performance status 0-1. Under full vitamin supplementation, pemetrexed was intravenously administered on Day 1 of a 21-day cycle, followed by cisplatin. A cohort of six patients, starting from pemetrexed 500 mg/m(2) and cisplatin 75 mg/m(2) (Level 1), were studied in the dose-escalation Phase I (Step 1). The RD determined in Step 1 was carried forward into Phase II (Step 2). Planned number of patients treated with Pem/Cis was 18-38. RESULTS: In Step 1, 13 patients were enrolled: seven in Level 1 and six in Level -1 (pemetrexed 500 mg/m(2), cisplatin 60 mg/m(2)). Two of six evaluable patients had dose-limiting toxicities (pneumonitis and neutropenia) in Level 1, establishing Level 1 as the RD. In Step 2, 12 patients were enrolled, for a total of 19 patients treated at the RD. Seven patients achieved a partial response among these patients, for a response rate of 36.8% (95% confidence interval: 16.3-61.6); overall survival was 7.3 months. One drug-related death occurred due to worsening of a pre-existing pneumonia. Common grade 3/4 toxicities were neutropenia and decreased-hemoglobin. CONCLUSION: The Pem/Cis combination provides promising activity and an acceptable safety profile for chemonaive Japanese MPM patients with the same recommend dosage and schedule used in rest of the world. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 64 1 2 3 4 > Last >> (1580 articles found)

      
 ESRNexus is provided as a service by TrialStat Corporation. ESRNexus is a registered trademark of TrialStat Corporation. Copyright 2008. View a list of all articles here