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1.
Philos Trans A Math Phys Eng Sci ; 380(2239): 20210278, 2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36335946

RESUMO

Speed is the key to further advances in technology. For example, quantum technologies, such as quantum computing, require fast manipulations of quantum systems in order to overcome the effect of decoherence. However, controlling the speed of quantum dynamics is often very difficult due to both the lack of a simple scaling property in the dynamics and the infinitely large parameter space to be explored. Therefore, protocols for speed control based on understanding of the dynamical properties of the system, such as non-trivial scaling property, are highly desirable. Fast-forward scaling theory (FFST) was originally developed to provide a way to accelerate, decelerate, stop and reverse the dynamics of quantum systems. FFST has been extended in order to accelerate quantum and classical adiabatic dynamics of various systems including cold atoms, internal state of molecules, spins and solid-state artificial atoms. This paper describes the basic concept of FFST and reviews the recent developments and its applications such as fast state-preparations, state protection and ion sorting. We introduce a method, called inter-trajectory travel, recently derived from FFST. We also point out the significance of deceleration in quantum technology. This article is part of the theme issue 'Shortcuts to adiabaticity: theoretical, experimental and interdisciplinary perspectives'.

2.
Pharmazie ; 74(9): 566-569, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31484599

RESUMO

Patients receiving cancer chemotherapy may experience a number of potentially severe adverse drug reactions. It is crucial for all members of the health care team to monitor the effect of medicines on the patient to ensure the safety and efficacy of the chemotherapy. The present study prepared medication instruction sheets (MISs) on hematological malignancy and conducted a questionnaire survey to verify their usefulness among physicians, dentists, and nurses. MISs were prepared for 103 chemotherapy and 44 pretreatment regimens for hematopoietic stem cell transplantation in the Department of Hematology at Kyushu University Hospital. Eight questions were prepared to investigate whether MISs could help physicians, dentists, and nurses manage cancer chemotherapy more safely, effectively, and efficiently, as well as in the sharing of information. A total of 35 medical staff working in inpatient wards, including 8 physicians, 3 dentists, and 24 nurses, participated in the questionnaire survey. All of the staff responded to the questionnaire survey, which showed that the MISs were favorably accepted by the participants. There was no negative opinion on the management of chemotherapy using the MISs. The MIS was a useful tool for sharing information on cancer chemotherapy between patients and medical staff and for enabling efficient management, thereby improving the safety and efficacy of treatment.


Assuntos
Antineoplásicos/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Neoplasias/tratamento farmacológico , Equipe de Assistência ao Paciente/normas , Antineoplásicos/efeitos adversos , Odontólogos/estatística & dados numéricos , Serviços de Informação sobre Medicamentos , Rotulagem de Medicamentos , Humanos , Enfermeiras e Enfermeiros/estatística & dados numéricos , Médicos/estatística & dados numéricos , Inquéritos e Questionários
3.
Allergol Immunopathol (Madr) ; 46(5): 482-490, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29786518

RESUMO

BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). RESULTS: Peach-allergic patients (n=27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n=17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P<0.05). CONCLUSIONS: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction.


Assuntos
Antígenos de Plantas/imunologia , Hipersensibilidade Alimentar/diagnóstico , Imunoglobulina E/sangue , Prunus persica/efeitos adversos , Adolescente , Adulto , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/efeitos adversos , Proteínas de Transporte/administração & dosagem , Proteínas de Transporte/efeitos adversos , Proteínas de Transporte/imunologia , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Hipersensibilidade Alimentar/sangue , Hipersensibilidade Alimentar/imunologia , Giberelinas/administração & dosagem , Giberelinas/efeitos adversos , Giberelinas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/imunologia , Adulto Jovem
4.
Clin Exp Immunol ; 190(1): 54-67, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28640392

RESUMO

Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)-/- and myeloid differentiation primary response gene 88 (MyD88)-/- mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9-/- mice but not in MyD88-/- mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.


Assuntos
Arterite/tratamento farmacológico , Inibidores de Calcineurina/uso terapêutico , Endotélio Vascular/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Fator 88 de Diferenciação Mieloide/metabolismo , Oligopeptídeos/uso terapêutico , Animais , Proteínas Adaptadoras de Sinalização CARD/genética , Vasos Coronários/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos SCID , Fator 88 de Diferenciação Mieloide/genética , Células RAW 264.7 , Transdução de Sinais
5.
Ann Oncol ; 27(3): 480-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26704052

RESUMO

BACKGROUND: We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. PATIENTS AND METHODS: Records of more than 300,000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21,755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. RESULTS: pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10,973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. CONCLUSION: We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Trastuzumab/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Feminino , Humanos , Hibridização in Situ Fluorescente , Japão , Pessoa de Meia-Idade , Receptor ErbB-2/biossíntese , Receptor ErbB-2/genética , Sistema de Registros , Resultado do Tratamento
6.
Eur J Neurol ; 22(2): 299-304, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25264295

RESUMO

BACKGROUND AND OBJECTIVES: Several symptoms and signs are characteristic of multiple sclerosis (MS) such as Lhermitte's sign, Uhthoff's phenomenon and painful tonic seizure. Neuromyelitis optica (NMO) is another inflammatory disease of the central nervous system, and most of the opticospinal form of MS is thought to be NMO. This study aimed to investigate the frequencies of symptoms and signs, previously regarded as characteristic of MS, in NMO and MS patients. METHODS: Consecutive Japanese NMO-plus patients [NMO (n = 30) or partial NMO (n = 18)] and MS patients (n = 128) seen at Chiba University Hospital between 2011 and 2012 were investigated for the frequencies of symptoms and signs characteristic of MS. Logistic regression analyses were used to identify factors that distinguished NMO-plus from MS. RESULTS: Univariate analyses revealed that tonic seizures, Lhermitte's sign, persistent pain, fatigue and girdle sensation were more frequent in NMO-plus patients than in MS patients. Multivariate logistic regression analysis showed that paroxysmal itching, Uhthoff's phenomenon, Lhermitte's sign and girdle sensation were more characteristic of NMO-plus than of MS. CONCLUSIONS: Several classical MS symptoms and signs are more frequent in NMO patients than MS patients, which may be caused by the differences in the severity of inflammation, and localization and extensiveness of demyelinated lesions.


Assuntos
Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Neuromielite Óptica/fisiopatologia , Adulto , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Neuromielite Óptica/epidemiologia
7.
Asian-Australas J Anim Sci ; 28(1): 14-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25557671

RESUMO

The genetic diversity of native chicken populations from Myanmar, Thailand, and Laos was examined by using 102 insertion and/or deletion (indels) markers. Most of the indels loci were polymorphic (71% to 96%), and the genetic variability was similar in all populations. The average observed heterozygosities (H O ) and expected heterozygosities (H E ) ranged from 0.205 to 0.263 and 0.239 to 0.381, respectively. The coefficients of genetic differentiation (Gst) for all cumulated populations was 0.125, and the Thai native chickens showed higher Gst (0.088) than Myanmar (0.041) and Laotian (0.024) populations. The pairwise Fst distances ranged from 0.144 to 0.308 among populations. A neighbor-joining (NJ) tree, using Nei's genetic distance, revealed that Thai and Laotian native chicken populations were genetically close, while Myanmar native chickens were distant from the others. The native chickens from these three countries were thought to be descended from three different origins (K = 3) from STRUCTURE analysis. Genetic admixture was observed in Thai and Laotian native chickens, while admixture was absent in Myanmar native chickens.

8.
J Clin Pharm Ther ; 39(2): 175-80, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24438433

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Decline in research and development (R&D) productivity and changes in the business environment have led to pharmaceutical company management to strive to improve R&D productivity. This decline is widely considered to be a major cause of industry consolidation and has received increased scholarly attention. This study aims to construct an R&D productivity map to visualize the industry's R&D productivity and to identify similarity in corporate actions with a view to investigate whether there is a relationship between deterioration in R&D productivity and industry consolidation. METHODS: Research and development productivity is decomposed into two subprocesses to measure productivity: R&D efficiency and R&D effectiveness, and scores were calculated using a two-stage data envelopment analysis (DEA). The map is then constructed by projecting outputs. To identify any relationship between DEA scores and merger and acquisition transactions, a multiple regression model is employed. RESULTS AND DISCUSSION: Data on 21 global pharmaceutical companies, statistical results indicated that companies with lower R&D efficiency scores were more likely to engage in consolidation. Three US companies that were least successful in terms of R&D effectiveness, as measured by our indicators, were either acquired or changed their business model. CONCLUSION: The R&D productivity map is a useful means for visualizing productivity among companies. By grouping companies into four groups, behavioural commonalities can be observed. The R&D productivity map should be useful for monitor the industry's productivity and help to improve it.


Assuntos
Indústria Farmacêutica/organização & administração , Eficiência Organizacional , Pesquisa/organização & administração , Indústria Farmacêutica/economia , Indústria Farmacêutica/tendências , Humanos , Análise de Regressão , Pesquisa/economia , Pesquisa/tendências
9.
Clin Exp Immunol ; 172(1): 37-43, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23480183

RESUMO

High mobility group box 1 (HMGB1) is an established inflammatory mediator when released from cells. Recent studies have implicated extracellular HMGB1 in the pathogenesis of various autoimmune diseases. The objective of this study was to determine whether HMGB1 could be a therapeutic target for experimental autoimmune encephalomyelitis (EAE). In this study, an anti-HMGB1 monoclonal antibody was injected intraperitoneally into a mouse model of EAE. We also measured serum cytokines levels in EAE and anti-HMGB1 monoclonal antibody-treated EAE. As a result, intraperitoneal injection of an anti-HMGB1 monoclonal antibody ameliorated the clinical and pathological severity of EAE and attenuated interleukin-17 up-regulation in serum. In conclusion, HMGB1 is involved in EAE pathogenesis and could trigger inflammation in the central nervous system. The novel aspect of this study is the demonstration that anti-HMGB1 ameliorates EAE. HMGB1 may be a novel therapeutic strategy for multiple sclerosis.


Assuntos
Anticorpos Monoclonais/farmacologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Proteína HMGB1/antagonistas & inibidores , Bainha de Mielina/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/sangue , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/genética , Proteína HMGB1/imunologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Injeções Intraperitoneais , Interleucina-17/sangue , Interleucina-17/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Bainha de Mielina/imunologia , Bainha de Mielina/patologia , Fármacos Neuroprotetores/imunologia , Índice de Gravidade de Doença , Medula Espinal/imunologia , Medula Espinal/patologia
10.
J Clin Pharm Ther ; 38(1): 62-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23057528

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The increasing cost of drug research and development and the decreasing number of new drugs being launched are serious issues for pharmaceutical companies. Biomarkers for predicting drug effectiveness are regarded as useful tools for combating these trends. However, the extent to which these biomarkers actually help in improving drug development is unclear. Here, we investigated the efficiency of biomarker usage in oncology drug development by focusing on stratification markers. METHODS: Anti-tumour agents for which clinical studies were initiated between 1998 and 2009 were identified using commercially available data sources, and clinical trials registered in ClinicalTrials.gov were examined to identify the use of stratification marker. Phase transition probability for each clinical phase was calculated and analysed along with various other factors that may affect the efficiency of the development process. RESULTS AND DISCUSSION: Of 908 anti-tumour agents identified, 121 (13·3%) utilized stratification markers in their clinical studies. Phase I, II and III transition probabilities for all agents were 76·4%, 50·8% and 58·5%, respectively. Corresponding Phase I, II and III transition probabilities of agents developed with stratification markers of 90·4%, 69·0% and 85·0%, respectively, were significantly higher than those for agents without stratification markers. Orphan designation positively affected phase transition probabilities of agents without stratification markers in all phases, while it did not affect transition probabilities of agents with stratification markers, except for Phase II. This shows that stratification markers help improve the probability of success in the development of agents without orphan designation. WHAT IS NEW AND CONCLUSION: Stratification markers contribute to improving the efficiency of development of anti-cancer drugs. The majority of non-orphan drugs are still being developed without stratification markers. Finding reliable stratification markers for all drugs should improve the success rates in drug development.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores/metabolismo , Desenho de Fármacos , Ensaios Clínicos como Assunto/métodos , Indústria Farmacêutica/métodos , Humanos , Neoplasias/tratamento farmacológico , Produção de Droga sem Interesse Comercial/métodos
11.
Environ Toxicol ; 28(1): 21-30, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21384493

RESUMO

Chlorinated benz[a]anthracenes (Cl-BaA) are halogenated aromatic compounds (typified by dioxins) found in the environment at relatively high concentrations. Fischer 344 rats were intragastrically administered 0, 1, or 10 mg of Cl-BaA or its parent compound benz[a]anthracene (BaA) per kg of body weight for 14 consecutive days. Both chemicals at 10 mg/kg/day inhibited the gain in body weight, and consequent increase in relative liver weight. Hepatic gene expression of cytochrome P450 (CYP) 1A1, 1A2, and 1B1 was significantly stimulated by administration of BaA (10 mg/kg/day) compared with the control. After administration of Cl-BaA, only the CYP1A2 gene was significantly induced, even at the lower dosage; CYP1A1 and 1B1 mRNA levels remained unchanged in Cl-BaA-treated rats compared with controls. To elucidate the role of such Cl-BaA exposure and induced CYPs at toxicity onset, we investigated the mutagenicity of BaA and Cl-BaA using Salmonella typhimurium TA98 and TA100. BaA and Cl-BaA at 10 µg/plate produced positive results in both strains in the presence of rat S-9. Incubation of Cl-BaA with recombinant rat CYP1A2 produced a significantly higher number of revertant colonies in TA98 and TA100 than in controls, but no such change was observed for BaA. In conclusion, BaA changes its own physiological and toxicological actions by its chlorination; (1) daily exposure to Cl-BaA selectively induces hepatic CYP1A2 in rats and (2) Cl-BaA induces frameshift mutations in the presence of CYP1A2, although BaA does not exert mutagenicity. This indicates that CYP1A2 may metabolize Cl-BaA to active forms.


Assuntos
Benzo(a)Antracenos/toxicidade , Fígado/efeitos dos fármacos , Mutagênicos/toxicidade , Salmonella typhimurium/efeitos dos fármacos , Animais , Hidrocarboneto de Aril Hidroxilases/metabolismo , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2 , Citocromo P-450 CYP1B1 , Citocromos/metabolismo , Mutação da Fase de Leitura , Regulação da Expressão Gênica/efeitos dos fármacos , Halogenação , Fígado/metabolismo , Masculino , Testes de Mutagenicidade , Ratos , Ratos Endogâmicos F344 , Salmonella typhimurium/metabolismo
12.
Diabetologia ; 55(1): 183-93, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21927895

RESUMO

AIMS/HYPOTHESIS: Although myostatin-null (Mstn (-/-)) mice fail to accumulate fat in adipose tissue when fed a high-fat diet (HFD), little is known about the molecular mechanism(s) behind this phenomenon. We therefore sought to identify the signalling pathways through which myostatin regulates accumulation and/or utilisation of fat. METHODS: Wild-type, Mstn (-/-) and wild-type mice treated with soluble activin type IIB receptor (sActRIIB) were fed a control chow diet or an HFD for 12 weeks. Changes in gene expression were measured by microarray and quantitative PCR. Histological changes in white adipose tissue were assessed together with peripheral tissue fatty acid oxidation and changes in circulating hormones following HFD feeding. RESULTS: Our results demonstrate that inactivation of myostatin results in reduced fat accumulation in mice on an HFD. Molecular analysis revealed that metabolic benefits, due to lack of myostatin, are mediated through at least two independent mechanisms. First, lack of myostatin increased fatty acid oxidation in peripheral tissues through induction of enzymes involved in lipolysis and in fatty acid oxidation in mitochondria. Second, inactivation of myostatin also enhanced brown adipose formation in white adipose tissue of Mstn (-/-) mice. Consistent with the above, treatment of HFD-fed wild-type mice with the myostatin antagonist, sActRIIB, reduced the obesity phenotype. CONCLUSIONS/INTERPRETATION: We conclude that absence of myostatin results in enhanced peripheral tissue fatty acid oxidation and increased thermogenesis, culminating in increased fat utilisation and reduced adipose tissue mass. Taken together, our data suggest that anti-myostatin therapeutics could be beneficial in alleviating obesity.


Assuntos
Tecido Adiposo Marrom/metabolismo , Adiposidade , Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos/metabolismo , Miostatina/antagonistas & inibidores , Obesidade/metabolismo , Receptores de Activinas Tipo II/química , Receptores de Activinas Tipo II/uso terapêutico , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/patologia , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/química , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Terapia de Alvo Molecular , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Miostatina/genética , Miostatina/metabolismo , Obesidade/etiologia , Obesidade/patologia , Obesidade/prevenção & controle , Oxirredução/efeitos dos fármacos , RNA Mensageiro/metabolismo , Solubilidade
13.
Br J Cancer ; 107(12): 2016-23, 2012 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-23169290

RESUMO

BACKGROUND: It has been a challenge to determine breast cancer clonality accurately. The aim of the present study was to assess methods using formalin-fixed paraffin-embedded (FFPE) tissue to differentiate new primary tumours from true recurrences that are associated with poorer prognoses and often require more aggressive treatment. METHODS: We investigated the novel method of analysing gene alterations of mitochondrial DNA D-loop region (GAMDDL) and compared it with the conventional method of analysing the X-chromosome-linked human androgen receptor (HUMARA). The FFPE sections of primary and secondary breast cancers, the non-neoplastic mammary gland, and lymph nodes were examined. RESULTS: Informative rates for HUMARA, GAMDDL, and combined analyses were 42.1%, 76.9%, and 89.5%, respectively. All of the 10 contralateral breast cancers were determined to be non-clonal. In contrast, 3 out of 8 (37.5%) of the ipsilateral secondary tumours shared a clonal origin with the primary tumour and were classified as true recurrences, whereas 4 out of 8 (50%) were classified as new primary tumours. CONCLUSION: GAMDDL analysis represents a novel and useful molecular method for examining the precise cell lineages of primary and secondary tumours, and was more accurate than HUMARA in determining clonality.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Células Clonais , DNA Mitocondrial/genética , Mutação , Recidiva Local de Neoplasia/diagnóstico , Segunda Neoplasia Primária/diagnóstico , Adulto , Idoso , Neoplasias da Mama/patologia , Cromossomos Humanos X , Células Clonais/patologia , Feminino , Formaldeído , Humanos , Microdissecção e Captura a Laser , Linfonodos/patologia , Glândulas Mamárias Humanas/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Segunda Neoplasia Primária/genética , Inclusão em Parafina , Reação em Cadeia da Polimerase , Receptores Androgênicos/genética
14.
Clin Genet ; 82(5): 425-32, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22575033

RESUMO

Auditory neuropathy is a hearing disorder characterized by normal outer hair cell function and abnormal neural conduction of the auditory pathway. Aetiology and clinical presentation of congenital or early-onset auditory neuropathy are heterogeneous, and their correlations are not well understood. Genetic backgrounds and associated phenotypes of congenital or early-onset auditory neuropathy were investigated by systematically screening a cohort of 23 patients from unrelated Japanese families. Of the 23 patients, 13 (56.5%) had biallelic mutations in OTOF, whereas little or no association was detected with GJB2 or PJVK, respectively. Nine different mutations of OTOF were detected, and seven of them were novel. p.R1939Q, which was previously reported in one family in the United States, was found in 13 of the 23 patients (56.5%), and a founder effect was determined for this mutation. p.R1939Q homozygotes and compound heterozygotes of p.R1939Q and truncating mutations or a putative splice site mutation presented with stable, and severe-to-profound hearing loss with a flat or gently sloping audiogram, whereas patients who had non-truncating mutations except for p.R1939Q presented with moderate hearing loss with a steeply sloping, gently sloping or flat audiogram, or temperature-sensitive auditory neuropathy. These results support the clinical significance of comprehensive mutation screening for auditory neuropathy.


Assuntos
Efeito Fundador , Estudos de Associação Genética/métodos , Perda Auditiva Central/epidemiologia , Perda Auditiva Central/genética , Proteínas de Membrana/genética , Adulto , Sequência de Aminoácidos , Povo Asiático/genética , Criança , Pré-Escolar , Conexina 26 , Conexinas/genética , Conexinas/metabolismo , Feminino , Testes Genéticos , Genótipo , Heterozigoto , Homozigoto , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , Prevalência , Conformação Proteica , Análise de Sequência de DNA
15.
Med Phys ; 39(7): 4414-22, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22830774

RESUMO

PURPOSE: The purpose of this study is to propose a microfocus x-ray imaging technique for observing the internal structure of small radioactive sources and evaluating geometrical errors quantitatively, and to apply this technique to traceable pointlike (22)Na sources, which were designed for positron emission tomography calibration, for the purpose of quality control of the pointlike sources. METHODS: A microfocus x-ray imaging system with a focus size of 0.001 mm was used to obtain projection x-ray images and x-ray CT images of five pointlike source samples, which were manufactured during 2009-2012. The obtained projection and tomographic images were used to observe the internal structure and evaluate geometrical errors quantitatively. Monte Carlo simulation was used to evaluate the effect of possible geometrical errors on the intensity and uniformity of 0.511 MeV annihilation photon pairs emitted from the sources. RESULTS: Geometrical errors were evaluated with sufficient precision using projection x-ray images. CT images were used for observing the internal structure intuitively. As a result, four of the five examined samples were within the tolerance to maintain the total uncertainty below ±0.5%, given the source radioactivity; however, one sample was found to be defective. CONCLUSIONS: This quality control procedure is crucial and offers an important basis for using the pointlike (22)Na source as a basic calibration tool. The microfocus x-ray imaging approach is a promising technique for visual and quantitative evaluation of the internal geometry of small radioactive sources.


Assuntos
Imagens de Fantasmas/normas , Radiografia/instrumentação , Radiografia/normas , Radioisótopos de Sódio/análise , Radioisótopos de Sódio/normas , Desenho de Equipamento , Análise de Falha de Equipamento , Japão , Compostos Radiofarmacêuticos/análise , Compostos Radiofarmacêuticos/normas , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
J Clin Pharm Ther ; 37(5): 547-52, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22428857

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Concern about the drug lag, the delay in marketing approval between one country and another, for anticancer drugs has increased in Japan. Although a number of studies have investigated the drug lag, none has investigated it in relation to the transition of anticancer therapy from traditional cytotoxic drugs to molecularly targeted agents. Our aim was to investigate current trend in oncology drug lag between the US and Japan and identify oncology drugs approved in only one of the two countries. METHODS: Publicly and commercially available data sources were used to identify drugs approved in the US and Japan as of 31 December 2010 and the data used to calculate the drug lag for individual drugs. RESULTS AND DISCUSSION: Fifty-one drugs were approved in both the US and Japan, whereas 34 and 19 drugs were approved only in the US or Japan, respectively. Of the 19 drugs approved only in Japan, 12 had not been subject to development for a cancer indication in the US, and all were approved before 1996 in Japan. Of the 34 drugs approved only in the US, 20 had not been subject to development in Japan, and none was in the top 25 by annual US anticancer drug-class sales. For drugs approved in both countries, the mean approval lag of the molecularly targeted drugs (MTDs) was significantly shorter than that of the non-molecularly targeted drugs (non-MTDs) (3·3 vs. 5·4 years). Further, mean R&D time of the MTDs was significantly shorter than that of non-MTDs (10·0 vs. 13·7 years). The price of MTDs had increased on average by 6·6% annually in the US, whereas it had decreased on average by 4·3% biyearly in Japan. WHAT IS NEW AND CONCLUSION: The emergence of new molecularly targeted agents has contributed to reducing the approval lag, most likely due to improvements in R&D strategy.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Aprovação de Drogas , Descoberta de Drogas , Antineoplásicos/uso terapêutico , Humanos , Japão , Marketing , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Pesquisa , Fatores de Tempo , Estados Unidos
18.
Radiography (Lond) ; 28(4): 906-911, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35785641

RESUMO

INTRODUCTION: This study aims to predict endoleak after endovascular aneurysm repair (EVAR) using machine learning (ML) integration of patient characteristics, stent-graft configuration, and a selection of vessel lengths, diameters and angles measured using pre-operative computed tomography angiography (CTA). METHODS: We evaluated 1-year follow-up CT scans (arterial and delayed phases) in patients who underwent EVAR for the presence or absence of an endoleak. We also obtained data on the patient characteristics, stent-graft selection, and preoperative CT vessel morphology (diameter, length, and angle). The extreme gradient boosting (XGBoost) for the ML system was trained on 30 patients with endoleaks and 81 patients without. We evaluated 5217 items in 111 patients with abdominal aortic aneurysms, including the patient characteristics, stent-graft configuration and vascular morphology acquired using pre-EVAR abdominal CTA. We calculated the area under the curve (AUC) of our receiver operating characteristic analysis using the ML method. RESULTS: The AUC, accuracy, 95% confidence interval (CI), sensitivity, and specificity were 0.88, 0.88, 0.79-0.97, 0.85, and 0.91 for ML applying XGBoost, respectively. CONCLUSIONS: The diagnostic performance of the ML method was useful when factors such as the patient characteristics, stent-graft configuration and vessel length, diameter and angle of the vessels were considered from pre-EVAR CTA. IMPLICATIONS FOR PRACTICE: Based on our findings, we suggest that this is a potential application of ML for the interpretation of abdominal CTA scans in patients with abdominal aortic aneurysms scheduled for EVAR.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Algoritmos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aortografia/métodos , Prótese Vascular , Angiografia por Tomografia Computadorizada , Endoleak/diagnóstico por imagem , Endoleak/cirurgia , Humanos , Aprendizado de Máquina , Stents , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Radiography (Lond) ; 28(2): 440-446, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34844859

RESUMO

INTRODUCTION: To investigate how changing the injection duration at cardiac computed tomography angiography (CCTA) affects contrast enhancement in newborns and infants. METHODS: Included were 142 newborns and infants with confirmed congenital heart disease who underwent CCTA between January 2015 and December 2018. In group 1 (n = 71 patients), the injection duration was 8 s; in group 2 (n = 71) it was 16 s. Our findings were assessed by one-to-one matching analysis to estimate the propensity score of each patient. We compare the CT number for the pulmonary artery (PA), ascending aorta (AAO), left superior vena cava (SVC), AAO and PA enhancement ratio, and the scores for visualization between the two groups. RESULTS: In group 1, median CT number and ranges was 345 (211-591) HU in the AAO, 324 (213-567) HU in the PA, and 62 (1-70) HU in the SVC. These values were 465 (308-669) HU, 467 (295-638) HU, and 234 (67-443) HU, respectively, in group 2 (p < 0.05). The median score for volume-rendering visualization on 3D images of the CCTA was 2 in group 1 and 3 in group 2; the score for visualization of the left SVC of the maximum intensity projection images was 2 in group 1 and 3 in group 2 (p < 0.05). The CT number for the AAO and PA enhancement ratio was 15.2 in group 1 and 9.2 in group 2 (p < 0.05). CONCLUSION: The 16-sec injection protocol yielded significantly higher CT numbers for the AAO, PA, and the SVC than the 8-sec injection protocol; the visualization scores were also significantly higher in group 2. IMPLICATIONS FOR PRACTICE: In newborns and infants, the longer injection time for CCTA yields stable and higher contrast enhancement at identical CM concentrations.


Assuntos
Angiografia por Tomografia Computadorizada , Veia Cava Superior , Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste , Humanos , Lactente , Recém-Nascido , Artéria Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Veia Cava Superior/diagnóstico por imagem
20.
Radiologia (Engl Ed) ; 64(6): 525-532, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36402538

RESUMO

INTRODUCTION AND OBJECTIVES: Obtaining CCTA images with optimal injection location such as the arm or leg is important to avoid the artifacts caused by the CM. This study compares the computed tomography (CT) numbers and visualization scores of the three-dimensional (3D) images of the lumens of the blood vessels in the arm or leg during cardiac computed tomography angiography (CCTA) in neonatal and infant patients. PATIENTS OR MATERIALS AND METHODS: Between January 2017 and January 2020, 253 consecutive patients were considered for inclusion. We used the estimated propensity scores as a function of the demographic data, including age, body weight, and injection location (right or left side) in the arm (n = 58) and leg (n = 58) of neonatal and infant patients. We compared the mean CT numbers of the pulmonary artery, ascending aorta, and left superior vena cava; contrast-noise ratios (CNR); and visualization scores between the arm and leg as the injection locations. RESULTS: The mean CT numbers during CCTA for the arm and leg were 479.4 and 461.3 HU in the ascending aorta, 464.2 and 448.1 HU in the pulmonary artery, and 232.8 and 220.1 HU in the left superior vena cava, respectively. The mean image noise (SD) and CNR values, respectively, were 38.9 HU and 12.1 for the arm as the injection location and 39.1 HU and 12.3 for the leg as the injection location. The median visualization scores of volume rendering of the 3D images were 3.0 and 3.0 for the arm and leg injection sites, respectively. There were no significant differences in the mean CT numbers of the ascending aorta, pulmonary artery, and left superior vena cava; SD value; CNR; and visualization scores between the arm and leg injection locations. CONCLUSIONS: The CT numbers of the lumen of the blood vessel and visualization scores of the 3D images of the arm and leg injection locations are equal during CCTA in neonatal and infant patients with congenital heart disease.


Assuntos
Meios de Contraste , Veia Cava Superior , Humanos , Lactente , Recém-Nascido , Braço/diagnóstico por imagem , Perna (Membro) , Tomografia Computadorizada por Raios X/métodos
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