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1.
Chaos ; 30(6): 063150, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32611115

RESUMO

We study the chaotic dynamics of graphene structures, considering both a periodic, defect free, graphene sheet and graphene nanoribbons (GNRs) of various widths. By numerically calculating the maximum Lyapunov exponent, we quantify the chaoticity for a spectrum of energies in both systems. We find that for all cases, the chaotic strength increases with the energy density and that the onset of chaos in graphene is slow, becoming evident after more than 104 natural oscillations of the system. For the GNRs, we also investigate the impact of the width and chirality (armchair or zigzag edges) on their chaotic behavior. Our results suggest that due to the free edges, the chaoticity of GNRs is stronger than the periodic graphene sheet and decreases by increasing width, tending asymptotically to the bulk value. In addition, the chaotic strength of armchair GNRs is higher than a zigzag ribbon of the same width. Furthermore, we show that the composition of 12C and 13C carbon isotopes in graphene has a minor impact on its chaotic strength.

2.
Minerva Anestesiol ; 80(9): 984-91, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24280816

RESUMO

BACKGROUND: The association of depression and hospital length of stay (LOS) has rarely been examined in surgical patients outside of cardiovascular surgery. This study investigates whether clinically significant preoperative depression shows an independent association with LOS in patients from various surgical fields after adjusting for age, gender and important somatic factors. METHODS: A total of 2624 surgical patients were included in this prospective observational study. Data were collected before the preoperative anesthesiological examination within a computer-assisted psychosocial self-assessment including screening for depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on peri- and postoperative somatic parameters were obtained from the electronic patient management system of the hospital six months after the preoperative assessment. RESULTS: LOS of patients with clinically significant depression (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of patients without depression (N.=2328; median: 4 days, interquartile range: 2-6 days) (P<0.001). A multivariate logistic regression model with the binary dependent variable 'above versus below or equal to the median LOS' revealed that the significant association between depression and LOS persisted (OR: 1.822 [95% CI 1.360-2.441], P<0.001) when simultaneously including the covariates age, gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM operative severity rating. CONCLUSION: Data suggest that the association of depression and LOS is independent of the impact of age, gender, surgical field, preoperative physical health, severity of medical comorbidity and extent of surgical procedure. Integration of depression therapy into routine care of surgical patients might be an option to improve outcomes.


Assuntos
Depressão/psicologia , Período Pré-Operatório , Procedimentos Cirúrgicos Operatórios/psicologia , Adulto , Comorbidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos
3.
Zentralbl Chir ; 138(1): 45-52, 2013 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22403014

RESUMO

BACKGROUND: The question of whether a medical care unit is an appropriate tool for outpatient care has been discussed for a long time. Our aim is to investigate whether the MCU is an effective instrument for outpatient care and adequate performance-related remuneration. MATERIAL AND METHODS: This retro- and prospective overview of the work included statements on legal foundations for medical care units, for reimbursement of services in medical care units, the development of medical care centres in Germany and a listing of the specific advantages and disadvantages of an MCU. This article focuses on the generally applicable facts and complements them with examples from general, visceral and vascular surgery. The main quantitative data on medical centre statistics come from different publications of the National Association of Statutory Health Insurance for Physicians. RESULTS: From a legal point of view the instrument MCU allows the participating of ambulatory and stationary care in the framework of medical care contracts. This has been especially extended for stationary applications, including the spectrum of possibilities that can contribute under certain circumstances for the provision of medical care in underdeveloped regions. Freelancers can benefit primarily from financial risk and minimising bureaucratic routine. The remuneration for services performed in the MCU is analogous to that of other ambulatory care providers. Basically, there are no disadvantages, but a greater design freedom and opportunities for the generation of aggregates are visible. The number of MCU in Germany has quadrupled in the last five years, indicating an establishment of an outpatient care landscape. MCU offers from the patient's perspective, providers and policy specific advantages and disadvantages. Indeed the benefits outweigh the disadvantages, but this is not yet verified by qualitative studies. CONCLUSION: The question of the appropriateness of medical care units as outpatient care instrumentation must be considered differentially. Under current conditions it appears suitable for ensuring the MCU and the supplement of care supply. Whether a value can be generated in the quality of care of patients, however, has to be examined separately, as there are no valid data so far. The same applies to economic assessments of costs and benefits from an economic perspective.


Assuntos
Programas Nacionais de Saúde/economia , Ambulatório Hospitalar/economia , Ambulatório Hospitalar/organização & administração , Reembolso de Incentivo/economia , Remuneração , Serviços Contratados/economia , Serviços Contratados/legislação & jurisprudência , Comportamento Cooperativo , Análise Custo-Benefício , Cirurgia Geral/economia , Cirurgia Geral/legislação & jurisprudência , Alemanha , Humanos , Comunicação Interdisciplinar , Programas Nacionais de Saúde/legislação & jurisprudência , Ambulatório Hospitalar/legislação & jurisprudência , Estudos Prospectivos , Reembolso de Incentivo/legislação & jurisprudência , Estudos Retrospectivos , Especialidades Cirúrgicas/economia , Especialidades Cirúrgicas/legislação & jurisprudência , Procedimentos Cirúrgicos Vasculares/economia , Procedimentos Cirúrgicos Vasculares/legislação & jurisprudência , Vísceras/cirurgia
4.
Psychol Health ; 27(11): 1291-307, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22472171

RESUMO

Hospital treatments are assumed to be a 'teachable moment'. This phenomenon, however, is only poorly conceptualised and untested. A stage-theoretical perspective implies that a cueing event such as hospital treatments is a teachable moment if a stage progression, change of cognitions, or both occur. This concept is examined in a cross-sectional study by comparing smokers in two treatment settings, an emergency department (ED) and inpatient treatment after elective surgery, with smokers in a control setting. Setting differences were hypothesised in stage distribution, and levels of and stage differences in social-cognitive factors under control for possible confounders. Stage, social-cognitive factors and possible confounders were assessed in 185 ED smokers, 193 inpatient smokers and 290 control smokers. Compared to control smokers, ED and inpatient smokers were in higher stages; they perceived fewer risks and cons; inpatient smokers reported more concrete plans. Stage differences in self-efficacy among ED and inpatient smokers differed from those among control smokers, but the former corresponded more strongly to the theoretical stage assumptions. The results suggest that hospital treatments lead to a stage progression and change of corresponding cognitions, and thus represent a 'teachable moment'. Stage-matched interventions should be provided but consider differences in cognitions to be effective.


Assuntos
Hospitalização , Educação de Pacientes como Assunto , Abandono do Hábito de Fumar , Adulto , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Motivação , Período Pós-Operatório , Autoeficácia , Adulto Jovem
5.
J Int Med Res ; 40(1): 194-203, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22429359

RESUMO

OBJECTIVE: Due to specific risks associated with illicit drug use, the preanaesthetic detection of illicit substances is essential. This prospective observational study evaluated oral fluid testing and self reporting of illicit drug use compared with confirmatory blood testing. METHODS: Consecutively enrolled preanaesthetic and emergency room patients (n=939) completed a paper-based lifestyle questionnaire. An oral fluid sample was obtained and analysed for illicit substance use by a point-of-care testing device (Dräger Drugtest® 5000). Patients who tested positive by self reporting or oral fluid testing underwent confirmatory blood testing (n=117). RESULTS: Self reporting revealed more overall illicit substance use and more users of cannabinoids, amphetamines, opioids, cocaine and benzodiazepines than oral fluid testing. Self reporting was more sensitive than blood testing for the detection of overall illicit substance use, and for use of cannabinoids and benzodiazepines. CONCLUSIONS: Self reporting revealed higher rates of illicit substance use than oral fluid testing in preanaesthetic patients, and may lead to more interventions and more appropriately tailored treatment and anaesthesia compared with oral fluid testing.


Assuntos
Líquidos Corporais/química , Boca/química , Medicação Pré-Anestésica , Detecção do Abuso de Substâncias/métodos , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Adulto , Demografia , Serviço Hospitalar de Emergência , Feminino , Alemanha , Testes Hematológicos , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Fatores de Risco , Autorrelato , Sensibilidade e Especificidade
6.
Med Klin Intensivmed Notfmed ; 106(2): 117-24, 2011 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-22038636

RESUMO

BACKGROUND: The aim of this post hoc study was to evaluate the association of substance use disorders (SUD) and residential neighborhood affiliation in a group of patients with minor injuries presenting to an inner-city emergency room (ER) in Berlin. METHODS: A total of 2,716 patients with minor injuries presenting to the ER were evaluated concerning alcohol use disorders (AUDIT, cut-off: males 8 points, females 5 points), smoking status, and illicit drug use in the past year. Information about residential area (zip code) and sociodemographics (paper-pencil questionnaire) were also obtained. RESULTS: With respect to residential area, significant differences concerning SUD were identified: from the perspective of the inner-city ER, living close to the ER was associated with substance misuse. Here, alcohol use disorders (AUD), smokers, and illicit drug use were found more frequently compared to patients living in the periphery of the city. In addition, patients living close to the ER were more often unemployed, had a lower income, or were students. CONCLUSION: There are differences in SUD with respect to residential area. However, in order to be able to draw reliable conclusions, an approach collecting representative data at the city district level as well as using a multicenter approach at the city ER level is necessary.


Assuntos
Alcoolismo/epidemiologia , Serviço Hospitalar de Emergência , Drogas Ilícitas , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , População Urbana/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adulto , Idoso , Berlim , Criança , Comorbidade , Estudos Transversais , Feminino , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Hospitais Universitários , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários
7.
Am J Med Genet A ; 155A(9): 2060-5, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21834043

RESUMO

We report on three patients from two families with apparently a novel clinical entity. The main features of which include unusual craniofacial dysmorphism with ptosis, prominent eyes, flat midface, Cupid's bow configuration of the upper lip, low-set, posteriorly rotated small ears, as well as conductive hearing loss, cleft palate, heart defect, and mild developmental delay. We suggest that this entity is an autosomal dominant disorder given the occurrence in a mother and daughter as well as in an unrelated boy.


Assuntos
Anormalidades Múltiplas , Transtornos Cromossômicos/genética , Deficiências da Aprendizagem , Adulto , Blefaroptose , Pré-Escolar , Fissura Palatina , Anormalidades Craniofaciais , Orelha/anormalidades , Anormalidades do Olho , Face/anormalidades , Feminino , Perda Auditiva , Cardiopatias Congênitas , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Síndrome
8.
Minerva Anestesiol ; 76(1): 29-37, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20130523

RESUMO

AIM: Illicit substance use (ISU) is a worldwide burden, and its prevalence in surgical patients has not been well investigated. Co-consumption of legal substances, such as alcohol and tobacco, complicates the perioperative management and is frequently underestimated during routine preoperative assessment. The aim of this study was to compare the anesthesiologists' detection rate of ISU during routine preoperative assessment with a computerized self-assessment questionnaire. METHODS: In total, 2,938 patients were included in this study. Prior to preoperative assessment, patients were asked to complete a computer-based questionnaire that addressed ISU, alcohol use disorder (AUDIT), nicotine use (Fagerström) and socio-economic variables (education, income, employment, partnership and size of household). Medical records were reviewed, and the anesthesiologists' detection of ISU was compared to the patients' self-reported ISU. RESULTS: Seven point five percent of patients reported ISU within the previous twelve months. ISU was highest in the age group between 18 and 30 years (26.4%; P<0.01). Patients reporting ISU were more often men than women (P<0.01), smokers (P<0.01) and tested positive for alcohol use disorder (P<0.01). Anesthesiologists detected ISU in one in 43 patients, whereas the computerized self-assessment reported it in one in 13 patients. The detection was best in the subgroup self-reporting frequent ISU (P<0.01). CONCLUSIONS: Anesthesiologists underestimate the prevalence of ISU. Computer-based self-assessment increases the detection of ISU in preoperative assessment and may decrease perioperative risk. More strategies to improve the detection of ISU as well as brief interventions for ISU are required in preoperative assessment clinics.


Assuntos
Anestesiologia , Cuidados Pré-Operatórios/métodos , Detecção do Abuso de Substâncias/métodos , Inquéritos e Questionários , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Detecção do Abuso de Substâncias/normas , Adulto Jovem
9.
J Appl Microbiol ; 109(2): 371-387, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20070440

RESUMO

The purpose of this article is to review coculture fermentations in industrial biotechnology. Examples for the advantageous utilization of cocultures instead of single cultivations include the production of bulk chemicals, enzymes, food additives, antimicrobial substances and microbial fuel cells. Coculture fermentations may result in increased yield, improved control of product qualities and the possibility of utilizing cheaper substrates. Cocultivation of different micro-organisms may also help to identify and develop new biotechnological substances. The relevance of coculture fermentations and the potential of improving existing processes as well as the production of new chemical compounds in industrial biotechnology are pointed out here by means of more than 35 examples.


Assuntos
Fermentação , Microbiologia Industrial/métodos , Técnicas de Cocultura , Aditivos Alimentares/metabolismo , Lignina/metabolismo
10.
Phys Rev E Stat Nonlin Soft Matter Phys ; 82(3 Pt 2): 036704, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21230210

RESUMO

We present and compare different numerical schemes for the integration of the variational equations of autonomous Hamiltonian systems whose kinetic energy is quadratic in the generalized momenta and whose potential is a function of the generalized positions. We apply these techniques to Hamiltonian systems of various degrees of freedom and investigate their efficiency in accurately reproducing well-known properties of chaos indicators such as the Lyapunov characteristic exponents and the generalized alignment indices. We find that the best numerical performance is exhibited by the "tangent map method," a scheme based on symplectic integration techniques which proves to be optimal in speed and accuracy. According to this method, a symplectic integrator is used to approximate the solution of the Hamilton equations of motion by the repeated action of a symplectic map S , while the corresponding tangent map TS is used for the integration of the variational equations. A simple and systematic technique to construct TS is also presented.

11.
Tob Control ; 18(4): 283-93, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19528043

RESUMO

OBJECTIVES: Emergency department (ED) patients show high smoking rates. The effects of ED-initiated tobacco control (ETC) on 7-day abstinence at 12 months were investigated. METHODS: A randomised controlled intention-to-treat trial (trials registry no.: ISRCTN41527831) was conducted with 1044 patients in an urban ED. ETC consisted of on-site counselling plus up to four telephone booster sessions. Controls received usual care. Analysis was by logistic regression. RESULTS: In all, 630 (60.7%) participants were males, the median age was 30 years (range 18-81) and the median smoking intensity was 15 (range 1-60) cigarettes per day. Overall, 580 study participants (55.6%) were unmotivated, 331 (31.7%) were ambivalent and 133 (12.7%) were motivated smokers. ETC (median time 30 (range 1-99) min) was administered to 472 (91.7% out of 515) randomised study participants. At follow-up, 685 study participants (65.6% of 1044) could be contacted. In the ETC group, 73 out of 515 (14.2%) in the ETC group were abstinent, whereas 60 out of 529 (11.3%) controls were abstinent (OR adjusted for age and gender = 1.31 (95% CI 0.91 to 1.89, p = 0.15). Stratified for motivation to change behaviour, the adjusted ORs for ETC versus usual care were OR = 1.00 (95% CI 0.57 to 1.76) in unmotivated smokers, respectively OR = 1.37 (95% CI 0.73 to 2.58) in ambivalent smokers and OR = 2.19 (95% CI 0.98 to 4.89) in motivated smokers, p for trend = 0.29. CONCLUSIONS: ETC, in the form of on-site counselling with up to four telephone booster sessions, showed no overall effect on tobacco abstinence after 12 months. A non-significant trend for a better performance of ETC in more motivated smokers was observed.


Assuntos
Serviço Hospitalar de Emergência , Abandono do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar , Adolescente , Adulto , Idoso , Aconselhamento/métodos , Feminino , Seguimentos , Alemanha , Hospitais Universitários , Linhas Diretas , Humanos , Análise de Intenção de Tratamento , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Motivação , Saúde da População Urbana/estatística & dados numéricos , Adulto Jovem
12.
Addict Behav ; 33(7): 906-18, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18384976

RESUMO

Every smoker should be offered smoking cessation treatment when they present for clinical care. The Readiness to Change-Smokers (RTC-S) questionnaire and the Heidelberg Smoking History (HSH) are brief questionnaires that divide patients into three stages. The purpose of this study was to prospectively compare the performance of each questionnaire at identifying patients who will successfully quit smoking within one year of Emergency Department (ED) discharge. Out of 1292 injured ED patients nearly half (n = 599, 46.4%) were identified as current smokers. Both questionnaires were given to all 599 subjects, and used to divide patients into three stages. At 12-months postdischarge 306 patients (51.1%) were contacted to determine smoking status. Patients were similarly classified by both tests in only 36% of cases. Concordance between tests was poor (kappa = 0.33). The RTC-S classified fewer patients as ready to quit (A = 13% vs. 22.2%). At 12 month follow-up, 55 patients (17.9%) had stopped smoking. The HSH was more successful to predict quitters. Multivariate logistic regression with respect to smoking cessation resulted in significant impact of HSH (p = 0.024).


Assuntos
Motivação , Abandono do Hábito de Fumar/psicologia , Fumar/psicologia , Inquéritos e Questionários/normas , Ferimentos e Lesões/psicologia , Adulto , Atitude Frente a Saúde , Tratamento de Emergência , Feminino , Seguimentos , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Estudos Prospectivos
13.
J Int Med Res ; 35(5): 609-14, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17900400

RESUMO

This cross-sectional investigation studied the association between substance use and patients' desire for autonomy in medical decision making (MDM) in two trauma settings. A total of 102 patients (age 42.7 +/- 17.4 years, 70.6% male) admitted to an orthopaedic service in Warsaw, Poland, and 1009 injured patients (age 34.6 +/- 12.8 years, 62.3% male) treated in an emergency department in Berlin, Germany, were enrolled. Patients' desire for autonomy in MDM was evaluated with the Decision Making Preference Scale of the Autonomy Preference Index. Substance use (hazardous alcohol consumption and/or tobacco use) and educational level were measured. Linear regression techniques were used to determine the association between substance use and desire for autonomy in MDM. Substance use was found to be independently associated with a reduced desire by the patient for autonomy in medical decision making. No differences in patients' desire for autonomy were observed between the study sites. Empowerment strategies that encourage smokers or patients with hazardous alcohol consumption to participate in MDM may increase the effectiveness of health promotion and injury prevention efforts in this population.


Assuntos
Consumo de Bebidas Alcoólicas , Tomada de Decisões , Liberdade , Fumar , Ferimentos e Lesões/psicologia , Humanos
14.
Acta Anaesthesiol Scand ; 50(8): 1019-26, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16923100

RESUMO

BACKGROUND: There is some evidence that patients' outcomes improve if they are involved in shared decision making (SDM). A chronic pain clinic or premedication visit could be adequate settings for the implementation of SDM. So far, the patients' preference for involvement in decision making and their desire for information have not been tested in anesthesiological settings. METHODS: A group of chronic pain patients was compared with a group of patients in the premedication visit with respect to SDM, the desire for information and perceived involvement in care. The autonomy preference index (API, measuring preference for involvement and desire for information) and the perceived involvement in care scale (PICS, measuring patients' perception of easier involvement by doctors and information exchange) were administered. RESULTS: In total, 190 chronic pain patients and 151 patients of premedication were included in this study. Patient of the premedication visit had significantly higher SDM scores. Desire for information was high, but there were no differences between groups. Younger patients [B (estimate) =- 0.3; 95% CI (-0.4) - (-0.1)], women (B = 10.9; 95% CI 6.3-15.4) and patients with higher educational level (B = 10.1; 95% CI 5.6-14.6) had more desire for SDM. PICS scores were basically influenced by groups: chronic pain patients felt more facilitated by doctors [B =- 0.185; 95% CI (-0.4) - (-0.1)] and had more information exchange [B =- 19.5; 95% CI (-15.8) - (-2.4)] than patients in the premedication visit. CONCLUSION: In both anesthesiological settings, the desire for information was high, but patients in the premedication visit had higher SDM scores, especially young female patients with higher educational level. Real patient-physician interaction showed that premedication patients felt less involved by doctors and had less information exchange compared with the chronic pain patients. Therefore, premedication visits should be focussed more on adequate information exchange and involvement of the patient in the shared decision making process.


Assuntos
Tomada de Decisões , Dor/psicologia , Educação de Pacientes como Assunto/estatística & dados numéricos , Participação do Paciente , Relações Médico-Paciente , Pré-Medicação/psicologia , Adulto , Idoso , Atitude , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Educação de Pacientes como Assunto/tendências , Inquéritos e Questionários
15.
Artigo em Alemão | MEDLINE | ID: mdl-15490085

RESUMO

The German Ministry for Health and Social Security is funding ten projects to introduce shared decision making into clinical practice. The medical problems the projects are focussing on were chosen from among various diseases (e. g. depression, multiple sclerosis, cancer). The ten projects achieved consensus on a core set of instruments for the measurement of process and outcome of the shared decision making. Instruments developed in German-speaking countries are currently not available. Thus, linguistic and cultural validation had to be performed for the core set instruments. The results of the data analysis as well as patient interviews demonstrate the need for improving these instruments. Therefore, the members of the methodological working group concentrated on the integration of these results in a new instrument. In a first step the construct of "shared decision making" was defined, followed by a definition of the process elements characterising shared decision making. Thereafter, items were developed on the basis of the process elements. The new instrument will now be validated for different diseases.


Assuntos
Tomada de Decisões , Participação do Paciente , Relações Médico-Paciente , Inquéritos e Questionários , Humanos , Fatores de Risco
16.
Oncogene ; 20(30): 4101-6, 2001 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-11494138

RESUMO

TNF-related apoptosis-inducing ligand (TRAIL) is a typical member of the tumor necrosis factor (TNF) ligand family that is expressed as a type II membrane protein (memTRAIL) and signals apoptosis via the death domain-containing receptors TRAIL-R1 and -2. Soluble recombinant derivatives of TRAIL (sTRAIL) are considered as novel tumors therapeutics because of their selective apoptosis inducing activity in a variety of human tumors but not in normal cells. Using antagonistic antigen-binding fragment (Fab) preparations of TRAIL-R1- and TRAIL-R2-specific antibodies, we demonstrate in this study that TRAIL-R1 becomes activated by both the soluble and the membrane-bound form of the ligand, whereas TRAIL-R2 becomes only activated by memTRAIL or soluble TRAIL secondarily cross-linked by antibodies. Furthermore, we show that the restricted signal capacity of sTRAIL can be readily converted into a fully signal competent memTRAIL-like molecule, i.e. a TRAIL-R2 stimulating ligand, by genetic fusion to an antibody derivative that allows antigen-dependent 'immobilization' of the fusion protein to cell surfaces. We conclude that antibody targeting-dependent activation can be used to design selective therapeutics derived of those ligands of the TNF family that are biologically inactive in their soluble form.


Assuntos
Antígenos de Superfície/imunologia , Glicoproteínas de Membrana/farmacologia , Receptores do Fator de Necrose Tumoral/fisiologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Animais , Especificidade de Anticorpos , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Células COS , Chlorocebus aethiops , Desenho de Fármacos , Células HeLa/efeitos dos fármacos , Humanos , Fragmentos Fab das Imunoglobulinas , Células Jurkat/efeitos dos fármacos , Células KB/efeitos dos fármacos , Ligantes , Glicoproteínas de Membrana/química , Proteínas de Membrana/química , Proteínas de Membrana/farmacologia , Proteínas de Neoplasias/efeitos dos fármacos , Proteínas de Neoplasias/imunologia , Proteínas de Neoplasias/fisiologia , Estrutura Terciária de Proteína , Receptores do Ligante Indutor de Apoptose Relacionado a TNF , Receptores do Fator de Necrose Tumoral/efeitos dos fármacos , Receptores do Fator de Necrose Tumoral/imunologia , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/fisiologia , Solubilidade , Ligante Indutor de Apoptose Relacionado a TNF , Fator de Necrose Tumoral alfa/química
17.
Eur J Biochem ; 268(6): 1730-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11248693

RESUMO

Four completely human antibody derivatives [single-chain-antibody fragments (scFvs)] with specificity for the general tumor stroma marker fibroblast activation protein (FAP) were isolated by guided selection. Highly diverse IgG, IgM and IgD isotypes comprising heavy-chain variable domain libraries were generated using cDNAs derived from diverse lymphoid organs of a multitude of donors. Three of the human scFvs were converted into bivalent minibodies and expressed in eukaryotic cells for further functional characterization. Binding-competition studies and analysis by fluorescence-activated cell sorting showed high-affinity binding (10--20 nM) for two clones and recognition of the same epitope as the murine guiding antibody. The minibodies were successfully used for immunohistology of a variety of human carcinoma biopsies, revealing specific staining of stromal fibroblasts. Therefore, they should be suitable for in vivo diagnostic and tumor-targeting studies and, because of their completely human origin, be superior to murine or humanized antibody derivatives.


Assuntos
Anticorpos Monoclonais/imunologia , Antígenos de Neoplasias , Biomarcadores Tumorais , Substâncias de Crescimento/imunologia , Serina Endopeptidases/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/química , Sequência de Bases , Ligação Competitiva , Primers do DNA , DNA Complementar , Endopeptidases , Gelatinases , Substâncias de Crescimento/química , Humanos , Imuno-Histoquímica , Proteínas de Membrana , Dados de Sequência Molecular , Neoplasias/imunologia , Homologia de Sequência de Aminoácidos , Serina Endopeptidases/química
18.
Zentralbl Gynakol ; 121(1): 41-5, 1999.
Artigo em Alemão | MEDLINE | ID: mdl-10091315

RESUMO

This report reflects the experience of accompanying HIV-infected women during the process of dying using their curriculi vitae as examples of different modes of dealing with fatal illness. The text contains paintings of past and contemporary art concerning death and eros and poetry as a form of therapy.


Assuntos
Síndrome da Imunodeficiência Adquirida/mortalidade , Arte , Atitude Frente a Morte , Poesia como Assunto , Síndrome da Imunodeficiência Adquirida/psicologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Fatores Sexuais , Assistência Terminal
19.
Arterioscler Thromb Vasc Biol ; 19(1): 47-53, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9888865

RESUMO

The expression of tissue factor (TF), the principal initiator of coagulation, is increased during inflammation and atherosclerosis. Both conditions are promoted by lysophosphatidylcholine (lysoPC). We observed in the present study that lysoPC (1 to 10 micromol/L) dose-dependently reduced TF activity in human monocytes, as elicited by lipopolysaccharide (LPS). Lysophosphatidylethanolamine (lysoPE) and other lysophospholipids did not affect LPS-induced TF activity of human monocytes. TF antigen expression as elicited by LPS was also lowered by lysoPC. Phospholipid analyses indicated a selective increase in the lysoPC content of the monocytes after preincubation with the lysophospholipid. LysoPC inhibited the TF activity of Mono Mac-6 cells to a similar extent as in the monocytes. LPS binding to plasma membrane receptors and internalization of LPS into monocytes were not affected by lysoPC. In contrast, LPS-mediated nuclear binding of nuclear factor-kappaB/Rel to a TF-specific kappaB site was inhibited by lysoPC. Induction of TF mRNA expression by LPS tended to be partially reduced by the lysophospholipid. Preincubation with lysoPC increased monocytic cAMP levels. Inhibition of adenylyl cyclase by pretreatment with 2'-deoxy-3'-adenosine monophosphate partially reversed the inhibition of TF activity promoted by lysoPC. In conclusion, lysoPC markedly decreases LPS-mediated TF expression of human monocytes, the effect probably being mediated by both transcriptional and posttranscriptional mechanisms. LysoPC may thus attenuate activation of coagulation during inflammation and atherosclerosis.


Assuntos
Lisofosfatidilcolinas/farmacologia , Monócitos/metabolismo , Tromboplastina/antagonistas & inibidores , Tromboplastina/metabolismo , Inibidores de Adenilil Ciclases , Northern Blotting , Bucladesina/farmacologia , Membrana Celular/metabolismo , AMP Cíclico/metabolismo , Nucleotídeos de Desoxiadenina/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Tromboplastina/genética
20.
Basic Res Cardiol ; 94(6): 472-80, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10651159

RESUMO

OBJECTIVE: Acute myocardial ischaemia leads to a transient sensitisation of adenylyl cyclase which may contribute to the occurrence of malignant arrhythmias and the propagation of myocardial necrosis. It is prevented by blockade of protein kinase C (PKC) which is activated in early ischaemia as shown by its translocation from the cytosol to the plasma membranes. Translocation of PKC may also occur in ischaemic preconditioning, a process thought to be induced by activation of adenosine A1 receptors. In this study it was investigated whether A1 adenosine receptors may be involved in the sensitisation of adenylyl cyclase and the activation of PKC induced by ischaemia. METHODS: Isolated rat hearts were perfused with the specific A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM) or adenosine (1 microM) prior to ischaemia induced by stop of perfusion for 5 and 10 min. Adenylyl cyclase activity was determined in plasma membranes stimulated by forskolin or stimulated via beta-receptors by isoproterenol. Total PKC activity was measured in purified plasma membranes and in the cytosolic fraction using histone III-S as a substrate. RESULTS: Myocardial ischaemia induced a beta-receptor-independent sensitisation of adenylyl cyclase (forskolin-stimulated activity 515+/-55 vs. 384+/-30 pmol/min/mg protein) which was completely blocked by pre-perfusion with DPCPX (385+/-23 vs. 386+/-24 pmol/min/mg protein). DPCPX alone did not alter the responsiveness of adenylyl cyclase to stimulation. The stimulated adenylyl cyclase activity was increased by 20 % after pre-perfusion with adenosine, mimicking the ischaemia-induced sensitisation. The effect of adenosine was not augmented by additional ischaemia. PKC activity was translocated from the cytosol to the plasma membranes by acute ischaemia, indicating an activation of the enzyme. This effect was completely abolished by DPCPX. CONCLUSION: These data demonstrate that in the rat heart the sensitisation of adenylyl cyclase in acute myocardial ischaemia is dependent on activation of A1 adenosine receptors. It is suggested that the sensitisation of adenylyl cyclase by adenosine or ischaemia might be mediated by an activation of PKC.


Assuntos
Adenilil Ciclases/metabolismo , Isquemia Miocárdica/metabolismo , Proteína Quinase C/metabolismo , Receptores Purinérgicos P1/metabolismo , Animais , Masculino , Isquemia Miocárdica/tratamento farmacológico , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
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