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1.
AIDS Care ; 33(10): 1286-1295, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33233939

RESUMO

Despite the availability of free and anonymous HIV testing almost 60% of Swedish patients are diagnosed late. Identifying predictors of different types of barriers could inform policy makers and health care of interventions to increase testing where needed. This cross-sectional study aimed to describe and analyze barriers to HIV testing as reported by Swedish patients newly diagnosed with HIV infection. N = 285 patients completed the 18-item Barriers to HIV Testing Scale - Karolinska Version. Descriptive analysis and logistic regressions were performed to assess the prevalence of barriers and to identify predictors for the different investigated barriers. Barriers to testing were reported by 60%. Approximately 67% of patients originating from Sweden, 50% from Sub-Saharan Africa and 75% from Eastern European/East Asian countries reported barriers. Patients who were younger and patients who self-initiated HIV testing, had greater odds of reporting a barrier than older individuals and those who were offered a test through screening or by a healthcare professional. To counteract barriers that still exist on an individual level, healthcare-initiated HIV testing could be offered more broadly and information about risks for transmission and effectiveness of HIV treatment still needs to be disseminated among both people born in Sweden and different migrant groups.


Assuntos
Infecções por HIV , Estudos Transversais , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Humanos , Programas de Rastreamento , Suécia/epidemiologia
2.
BMC Cancer ; 20(1): 722, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32758179

RESUMO

BACKGROUND: There is a lack of firm knowledge regarding sexual problems and fertility-related distress in young adults following a diagnosis with cancer. Establishing such understanding is essential to identify patients in need of specific support and to develop cancer care accordingly. This study protocol describes the Fex-Can Cohort study, a population-based prospective cohort study investigating sexual dysfunction and fertility-related distress in young adults diagnosed with cancer in Sweden. The primary objective of the study is to determine the prevalence and predictors of sexual dysfunction and fertility-related distress following a cancer diagnosis in young adulthood compared to prevalence rates for the general population. Further aims are to investigate the trajectories of these issues over time, the co-existence between sexual dysfunction and fertility-related distress, and the relation between these issues and body image, anxiety and depression, health-related quality of life, self-efficacy related to sexuality and fertility, and fertility-related knowledge. METHODS: Participants in the Fex-Can Cohort will be identified via the Swedish National Quality Registries for Brain Tumors, Breast Cancer, Gynecological Oncology, Lymphoma, and Testicular Cancer. All patients diagnosed at the ages of 18-39, during a period of 18 months, will be invited to participate. Established instruments will be used to measure sexual function (PROMIS SexFS), fertility-related distress (RCAC), body image (BIS), anxiety and depression (HADS), and health-related quality of life (QLQ-C30); Self-efficacy and fertility-related knowledge will be assessed by study-specific measures. The survey will be administered to participants at baseline (approximately 1.5 year after diagnosis) and at 3 and 5 years post-diagnosis. Registry data will be used to collect clinical variables. A comparison group of 2000 young adults will be drawn from the Swedish population register (SPAR) and subsequently approached with the same measures as the cancer group. DISCUSSION: The study will determine the prevalence and predictors of sexual dysfunction and fertility-related distress in young men and women with cancer. The findings will form a basis for developing interventions to alleviate sexual problems and fertility-related distress in young adults with cancer in the short and long term. TRIAL REGISTRATION: This is an observational cohort study and clinical trial registration was therefore not obtained.


Assuntos
Fertilidade , Neoplasias/complicações , Disfunções Sexuais Fisiológicas/etiologia , Saúde Sexual , Adulto , Fatores Etários , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Neoplasias/diagnóstico , Medidas de Resultados Relatados pelo Paciente , Prevalência , Estudos Prospectivos , Tamanho da Amostra , Disfunções Sexuais Fisiológicas/epidemiologia , Suécia/epidemiologia , Fatores de Tempo , Adulto Jovem
3.
J Sex Med ; 16(7): 1049-1059, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31255211

RESUMO

INTRODUCTION: The survival rates for testicular cancer are excellent; still, there is a lack of knowledge regarding important survivorship issues, such as sexual dysfunction and reproductive concerns. AIM: The aim of this study was to investigate the prevalence and predictors of sexual dysfunction and reproductive concerns and the potential association between these issues in young men ∼2 years after a diagnosis of testicular cancer. METHODS: Data were collected from 111 men (response rate = 50%) diagnosed with testicular cancer at age 16-39. Patients were identified via the Swedish National Quality Registry for Testicular Cancer and approached with a survey, including standardized measures of sexual function, reproductive concerns, body image, and health-related quality of life. The survey was sent to participants approximately 2 years after their cancer diagnosis. Clinical variables were collected from the registry. Predictors were identified by multivariable linear regression analyses. MAIN OUTCOME MEASURES: The main outcomes were sexual function, assessed with the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction measure version 2.0, and reproductive concerns, assessed with the Reproductive Concerns After Cancer scale. RESULTS: Sexual dysfunction was reported by 26% of men, and a high level of reproductive concerns was reported by 28%. Lower satisfaction with sex life was associated with older age (ß = -0.41), negative body image (ß = -0.42), not having a partner (ß = 4.8), and dissatisfaction with sex life before cancer (ß = 8.31). Negative body image was associated with reproductive concerns in the dimensions of fertility potential (ß = 0.06), partner disclosure (ß = 0.08), and child's health (ß = 0.07), whereas having had fertility preservation predicted higher levels of concerns with regard to personal health (ß = 0.52) and achieving pregnancy (ß = 0.53). Clinical variables did not predict either sexual function or reproductive concerns. CLINICAL IMPLICATIONS: Our results show that the majority of young men diagnosed with testicular cancer do not report sexual dysfunction or reproductive concerns 2 years after diagnosis. A sizeable minority, however, does report dysfunction or reproductive concerns, which should be recognized in the follow-up care of this population. STRENGTHS & LIMITATIONS: A strength of the study is the use of high-quality registry data and validated instruments. The lack of Swedish norms for sexual function and reproductive concerns is a possible limitation. CONCLUSION: A subgroup of young men treated for testicular cancer report sexual dysfunction or reproductive concerns approximately 2 years after diagnosis. Factors associated with these issues seem to mainly be psychological, rather than medical, nature. Ljungman L, Eriksson LE, Flynn KE, et al. Sexual Dysfunction and Reproductive Concerns in Young Men Diagnosed With Testicular Cancer: An Observational Study. J Sex Med 2019;16:1049-1059.


Assuntos
Fertilidade , Reprodução , Disfunções Sexuais Fisiológicas/epidemiologia , Neoplasias Testiculares/patologia , Adolescente , Adulto , Imagem Corporal , Feminino , Humanos , Masculino , Satisfação Pessoal , Gravidez , Prevalência , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Suécia , Adulto Jovem
4.
BMC Cancer ; 19(1): 344, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975116

RESUMO

BACKGROUND: This study protocol describes the clinical trial of the Fex-Can intervention, a web-based self-help program targeting sexual dysfunction and fertility-related distress. The psycho-educational intervention has been developed in collaboration with young patients with cancer and shown to be feasible. The primary objective is to determine whether the Fex-Can intervention, provided in addition to standard care, is superior to standard care in terms of reduction of sexual dysfunction and fertility-related distress directly after end of the 12-week program. The trial also aims to determine whether the intervention has an effect on the secondary outcomes including health-related quality of life, anxiety, depression, body image, fertility knowledge, and self-efficacy related to sexuality and fertility. METHODS: The trial has an randomized clinical trial (RCT) design with two parallel arms. The active groups receive either the version of the Fex-Can intervention targeting sexual problems or the version targeting fertility-related distress. Control groups receive standard care. Primary outcomes will be sexual function assessed with the Patient-Reported Outcomes Measurement Information System® Sexual Function and Satisfaction measure version 2.0 (SexFS) and fertility-related distress assessed with the Reproductive Concerns After Cancer scale (RCAC). The effect of the intervention will be evaluated directly after end of the program. Primary and secondary outcomes will also be assessed at the short- (12 weeks after end of program) and long-term (20 and 44 months after end of program) follow-up. At least 64 completers will be needed in each arm (total n = 256) to achieve adequate statistical power in the analyses. In order to increase the understanding of how the intervention brings about a possible change, semi-structured interviews will additionally be conducted with a purposeful sample shortly after completion of the intervention. DISCUSSION: If the Fex-Can intervention proves to be efficacious the necessary steps will be taken to implement it in routine care for young adults diagnosed with cancer. Healthcare could thereby be provided with an easily accessible, cost-effective intervention to offer to young adults suffering from fertility-related distress or sexual problems. TRIAL REGISTRATION: ISRCTN36621459 . Registered 25 January 2016.


Assuntos
Fertilidade , Neoplasias/psicologia , Educação de Pacientes como Assunto/métodos , Psicoterapia/métodos , Autogestão/métodos , Disfunções Sexuais Psicogênicas/reabilitação , Adulto , Ansiedade/psicologia , Ansiedade/reabilitação , Imagem Corporal/psicologia , Sobreviventes de Câncer/psicologia , Depressão/psicologia , Depressão/reabilitação , Feminino , Humanos , Internet , Masculino , Neoplasias/terapia , Psico-Oncologia/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoeficácia , Disfunções Sexuais Psicogênicas/psicologia , Sexualidade/psicologia , Estresse Psicológico/psicologia , Estresse Psicológico/reabilitação , Adulto Jovem
5.
Hum Reprod ; 29(12): 2704-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25344069

RESUMO

STUDY QUESTION: What do adolescent and young adult survivors of childhood cancer think about the risk of being infertile? SUMMARY ANSWER: The potential infertility, as well as the experience of having had cancer, affects well-being, intimate relationships and the desire to have children in the future. WHAT IS KNOWN ALREADY: Many childhood cancer survivors want to have children and worry about possible infertility. STUDY DESIGN, SIZE, DURATION: For this qualitative study with a cross-sectional design, data were collected through 39 online focus group discussions during 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cancer survivors previously treated for selected diagnoses were identified from The Swedish Childhood Cancer Register (16-24 years old at inclusion, ≥5 years after diagnosis) and approached regarding study participation. Online focus group discussions of mixed sex (n = 133) were performed on a chat platform in real time. Texts from the group discussions were analysed using qualitative content analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The analysis resulted in the main category Is it possible to have a baby? including five generic categories: Risk of infertility affects well-being, Dealing with possible infertility, Disclosure of possible infertility is a challenge, Issues related to heredity and Parenthood may be affected. The risk of infertility was described as having a negative impact on well-being and intimate relationships. Furthermore, the participants described hesitation about becoming a parent due to perceived or anticipated physical and psychological consequences of having had cancer. LIMITATIONS, REASONS FOR CAUTION: Given the sensitive topic of the study, the response rate (36%) is considered acceptable. The sample included participants who varied with regard to received fertility-related information, current fertility status and concerns related to the risk of being infertile. WIDER IMPLICATIONS OF THE FINDINGS: The results may be transferred to similar contexts with other groups of patients of childbearing age and a risk of impaired fertility due to disease. The findings imply that achieving parenthood, whether or not with biological children, is an area that needs to be addressed by health care services. STUDY FUNDING/COMPETING INTERESTS: The study was financially supported by The Cancer Research Foundations of Radiumhemmet, The Swedish Childhood Cancer Foundation and the Doctoral School in Health Care Science, Karolinska Institutet. The authors report no conflicts of interest.


Assuntos
Grupos Focais , Infertilidade/psicologia , Sobreviventes/psicologia , Adolescente , Estudos Transversais , Feminino , Preservação da Fertilidade/psicologia , Humanos , Masculino , Qualidade de Vida , Suécia , Adulto Jovem
6.
Scand J Rheumatol ; 41(5): 383-90, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22646821

RESUMO

OBJECTIVE: The aim of this study was to explore the most distressing symptoms of systemic lupus erythematosus (SLE) and determine how these relate to health-related quality of life (HRQoL), anxiety/depression, patient demographics, and disease characteristics (duration, activity, organ damage). METHODS: In a cross-sectional study, patients with SLE (n = 324, age 18-84 years) gave written responses regarding which SLE-related symptoms they experienced as most difficult. Their responses were categorized. Within each category, patients reporting a specific symptom were compared with non-reporters and analysed for patient demographics, disease duration, and results from the following questionnaires: the Medical Outcomes Study 36-item Short Form Health Survey (SF-36), the Hospital Anxiety and Depression Scale (HADS), the Systemic Lupus Activity Measure (SLAM), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology (SLICC/ACR) damage index. RESULTS: Twenty-three symptom categories were identified. Fatigue (51%), pain (50%), and musculoskeletal distress (46%) were most frequently reported. Compared with non-reporters, only patients reporting fatigue showed a statistically significant impact on both mental and physical components of HRQoL. Patients with no present symptoms (10%) had higher HRQoL (p < 0.001) and lower levels of depression (p < 0.001), anxiety (p < 0.01), and disease activity (SLAM) (p < 0.001). CONCLUSION: Fatigue, pain, or musculoskeletal distress dominated the reported symptoms in approximately half of the patients. Only patients reporting fatigue scored lower on both mental and physical aspects of HRQoL. Our results emphasize the need for further support and interventions to ease the symptom load and improve HRQoL in patients with SLE. Our findings further indicate that this need is particularly urgent for patients with symptoms of pain or fatigue.


Assuntos
Ansiedade/diagnóstico , Depressão/diagnóstico , Fadiga/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/complicações , Ansiedade/psicologia , Estudos Transversais , Depressão/complicações , Depressão/psicologia , Autoavaliação Diagnóstica , Fadiga/complicações , Fadiga/psicologia , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/psicologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
7.
Biochim Biophys Acta ; 1778(1): 206-13, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17967411

RESUMO

We investigated the nuclear localization-like sequence KKRPKP, corresponding to the residues 23-28 in the mouse prion protein (mPrP), for its membrane perturbation activity, by comparing effects of two mPrP-derived peptides, corresponding to residues 1-28 (mPrPp(1-28)) and 23-50 (mPrPp(23-50)), respectively. In erythrocytes, mPrPp(1-28) induced approximately 60% haemoglobin leakage after 30 min, whereas mPrPp(23-50) had negligible effects. In calcein-entrapping, large unilamellar vesicles (LUVs), similar results were obtained. Cytotoxicity estimated by lactate dehydrogenase leakage from HeLa cells, was found to be approximately 12% for 50 microM mPrPp(1-28), and approximately 1% for 50 microM mPrPp(23-50). Circular dichroism spectra showed structure induction of mPrPp(1-28) in the presence of POPC:POPG (4:1) and POPC LUVs, while mPrPp(23-50) remained a random coil. Membrane translocation studies on live HeLa cells showed mPrPp(1-28) co-localizing with dextran, suggesting fluid-phase endocytosis, whereas mPrPp(23-50) hardly translocated at all. We conclude that the KKRPKP-sequence is not sufficient to cause membrane perturbation or translocation but needs a hydrophobic counterpart.


Assuntos
Sinais de Localização Nuclear , Príons/química , Príons/metabolismo , Lipossomas Unilamelares/metabolismo , Sequência de Aminoácidos , Animais , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Fluoresceínas/metabolismo , Células HeLa , Hemoglobinas/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Microscopia Confocal , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/farmacologia , Proteínas Priônicas , Relação Estrutura-Atividade , Água/química
8.
Int J STD AIDS ; 18(3): 207-11, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17362557

RESUMO

Men who have sex with men (MSM) have an increased risk of contracting sexually transmitted diseases (STDs) and HIV. Studies of their health-related quality of life (HRQL) are uncommon, though such studies may provide additional knowledge that is of interest in counselling and care. The HRQL in MSM attending a clinic for STD- and HIV testing in Stockholm, Sweden, was investigated in 1996 and 2004, measured by means of the Swedish Health-Related Quality of Life questionnaire. The results were compared with those for men from a general Swedish population sample and with HIV-infected men. The HIV-negative MSM had significantly worse emotional wellbeing, satisfaction with family life, relation to their partner and general health perception, and better physical HRQL compared with the general Swedish population. There were no differences in the emotional and family dimensions between HIV-infected and HIV-negative MSM, but the HIV-negative group scored at a higher level in respect of their physical and general health than the HIV-infected group. No apparent differences over time were seen in the HIV-negative group. This study shows that psychosocial HRQL is lower for MSM than for a general male population sample, which calls for increased attention in the care of MSM patients.


Assuntos
Bissexualidade , Homossexualidade Masculina , Infecções Sexualmente Transmissíveis/psicologia , Adolescente , Adulto , Idoso , Instituições de Assistência Ambulatorial , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Suécia
9.
Biochem Biophys Res Commun ; 348(2): 379-85, 2006 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-16893522

RESUMO

A peptide derived from the N-terminus of the unprocessed bovine prion protein (bPrPp), incorporating the hydrophobic signal sequence (residues 1-24) and a basic domain (KKRPKP, residues 25-30), internalizes into mammalian cells, even when coupled to a sizeable cargo, and therefore functions as a cell-penetrating peptide (CPP). Confocal microscopy and co-localization studies indicate that the internalization of bPrPp is mainly through macropinocytosis, a fluid-phase endocytosis process, initiated by binding to cell-surface proteoglycans. Electron microscopy studies show internalized bPrPp-DNA-gold complexes residing in endosomal vesicles. bPrPp induces expression of a complexed luciferase-encoding DNA plasmid, demonstrating the peptide's ability to transport the cargo across the endosomal membrane and into the cytosol and nucleus. The novel CPP activity of the unprocessed N-terminal domain of PrP could be important for the retrotranslocation of partly processed PrP and for PrP trafficking inside or between cells, with implications for the infectivity associated with prion diseases.


Assuntos
Fragmentos de Peptídeos/metabolismo , Pinocitose/fisiologia , Príons/metabolismo , Androstadienos/farmacologia , Animais , Células CHO , Bovinos , Cricetinae , Cricetulus , Citocalasina D/farmacologia , Estrutura Terciária de Proteína , Transporte Proteico , Wortmanina
10.
Biochim Biophys Acta ; 1716(2): 126-36, 2005 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-16214105

RESUMO

Peptides derived from the unprocessed N-termini of mouse and bovine prion proteins (mPrPp and bPrPp, respectively), comprising hydrophobic signal sequences followed by charged domains (KKRPKP), function as cell-penetrating peptides (CPPs) with live cells, concomitantly causing toxicity. Using steady-state fluorescence techniques, including calcein leakage and polarization of a membrane probe (diphenylhexatriene, DPH), as well as circular dichroism, we studied the membrane interactions of the peptides with large unilamellar phospholipid vesicles (LUVs), generally with a 30% negative surface charged density, comparing the effects with those of the CPP penetratin (pAntp) and the pore-forming peptide melittin. The prion peptides caused significant calcein leakage from LUVs concomitant with increased membrane ordering. Fluorescence correlation spectroscopy (FCS) studies of either rhodamine-entrapping (REVs) or rhodamine-labeled (RLVs) vesicles, showed that addition of the prion peptides resulted in significant release of rhodamine from the REVs without affecting the overall integrity of the RLVs. The membrane leakage effects due to the peptides had the following order of potency: melittin>mPrPp>bPrPp>pAntp. The membrane perturbation effects of the N-terminal prion peptides suggest that they form transient pores (similar to melittin) causing toxicity in parallel with their cellular trafficking.


Assuntos
Membrana Celular/química , Príons/química , Animais , Biofísica/métodos , Proteínas de Transporte/química , Bovinos , Membrana Celular/metabolismo , Peptídeos Penetradores de Células , Dicroísmo Circular , Difusão , Difenilexatrieno/química , Fluoresceínas/química , Meliteno/química , Camundongos , Peptídeos/química , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Rodaminas/química , Espectrometria de Fluorescência , Espectrofotometria , Fatores de Tempo
12.
FEBS Lett ; 555(2): 371-4, 2003 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-14644445

RESUMO

We show for the first time that the secondary structure of the Alzheimer beta-peptide is in a temperature-dependent equilibrium between an extended left-handed 3(1) helix and a flexible random coil conformation. Circular dichroism spectra, recorded at 0.03 mM peptide concentration, show that the equilibrium is shifted towards increasing left-handed 3(1) helix structure towards lower temperatures. High resolution nuclear magnetic resonance (NMR) spectroscopy has been used to study the Alzheimer peptide fragment Abeta(12-28) in aqueous solution at 0 degrees C and higher temperatures. NMR translation diffusion measurements show that the observed peptide is in monomeric form. The chemical shift dispersion of the amide protons increases towards lower temperatures, in agreement with the increased population of a well-ordered secondary structure. The solvent exchange rates of the amide protons at 0 degrees C and pH 4.5 vary within at least two orders of magnitude. The lowest exchange rates (0.03-0.04 min(-1)) imply that the corresponding amide protons may be involved in hydrogen bonding with neighboring side chains.


Assuntos
Peptídeos beta-Amiloides/química , Fragmentos de Peptídeos/química , Dicroísmo Circular , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Temperatura
13.
Biophys Chem ; 103(3): 271-88, 2003 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-12727289

RESUMO

Cell-penetrating peptides (CPPs) are able to translocate and carry cargo molecules across cell membranes. Using fluorescence techniques (polarization and quenching) and CD spectroscopy we studied the interaction, conformation and topology of two such peptides, transportan and 'penetratin' (pAntp), and two variants of differing translocating abilities, with small phospholipid vesicles of varying charge density. The induced structure of transportan is always helical independent of vesicle surface charge. pAntp and its two variants interact significantly only with negatively charged vesicles. The induced secondary structure depends on membrane charge and lipid/peptide ratio. The degree of membrane perturbation, evidenced by fluorescence polarization, of pAntp and its variants is related to their secondary structure. In the helical state, the peptides have little effect on the membrane. Under conditions where pAntp and its variants are converted into beta-structures, they cause membrane perturbation. Oriented CD suggests that the two CPPs (pAntp and transportan) in their helical state lie along the vesicle surface, while the two pAntp variants appear to penetrate deeper into the membrane.


Assuntos
Proteínas de Transporte/química , Fosfolipídeos/química , Proteínas Recombinantes de Fusão/química , Sequência de Aminoácidos , Membrana Celular/química , Peptídeos Penetradores de Células , Dicroísmo Circular , Polarização de Fluorescência , Galanina , Micelas , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Espectrometria de Fluorescência , Marcadores de Spin , Eletricidade Estática , Propriedades de Superfície , Venenos de Vespas
14.
Biochem Biophys Res Commun ; 299(1): 85-90, 2002 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-12435392

RESUMO

The N-terminal (1-28) part of the mouse prion protein (PrP) is a cell penetrating peptide, capable of transporting large hydrophilic cargoes through a cell membrane. Confocal fluorescence microscopy shows that it transports the protein avidin (67kDa) into several cell lines. The (1-28) peptide has a strong tendency for aggregation and beta-structure formation, particularly in interaction with negatively charged phospholipid membranes. The findings have implications for how prion proteins with uncleaved signal peptides in the N-termini may enter into cells, which is important for infection. The secondary structure conversion into beta-structure may be relevant as a seed for the conversion into the scrapie (PrP(Sc)) form of the protein and its amyloidic transformation.


Assuntos
Membrana Celular/metabolismo , Príons/química , Príons/metabolismo , Sequência de Aminoácidos , Animais , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Camundongos , Microscopia Confocal , Dados de Sequência Molecular , Biossíntese Peptídica , Peptídeos/química , Proteínas PrPSc/metabolismo , Sinais Direcionadores de Proteínas , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Transporte Proteico , Fatores de Tempo , Células Tumorais Cultivadas
15.
Biochim Biophys Acta ; 1563(1-2): 53-63, 2002 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-12007625

RESUMO

The most commonly studied of the cell-penetrating peptides (CPP) is "penetratin" (pAntp), which functions as a carrier (vector), even for large hydrophilic (cargo) molecules. pAntp originates from the third helix of the Antennapedia homeodomain protein. The peptide is known to interact with negatively charged phospholipid vesicles, which leads to induction of secondary structure. In the present study, circular dichroism (CD) spectroscopy has been used to characterize the different secondary structures induced upon interaction with small unilamellar vesicles (SUVs) from mixtures of zwitterionic 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) and negatively charged 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG). The interaction was monitored using an electron paramagnetic resonance (EPR) spin probe attached to the peptide, and the intrinsic fluorophore (tryptophan). We measured the secondary structure as a function of surface charge density, total lipid-to-peptide (L/P) molar ratio, and salt concentration, for completely bound peptide. With vesicles from POPG/POPC in a molar ratio below 30:70, at a high L/P, the peptide adopts a mainly helical conformation. Increasing the charge density, at the same L/P, promotes a higher degree of beta-structure. At a fixed charge density, reducing the L/P also results in an alpha-->beta structure conversion. Hence, low membrane surface charge density and low pAntp concentration both favor a mainly helical conformation, while high charge density and pAntp concentration promote a dominating beta-structure. We conclude that pAntp, when residing at the surface of a membrane, is chameleon-like in terms of its induced structure.


Assuntos
Proteínas de Transporte/química , Vesículas Citoplasmáticas/química , Fosfolipídeos/química , Conformação Proteica , Peptídeos Penetradores de Células , Dicroísmo Circular , Espectroscopia de Ressonância de Spin Eletrônica , Fluorescência , Fragmentos de Peptídeos/química , Fosfatidilgliceróis , Estrutura Secundária de Proteína , Marcadores de Spin , Eletricidade Estática , Propriedades de Superfície
16.
Bioconjug Chem ; 12(6): 911-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11716681

RESUMO

Cellular translocation into a human Bowes melanoma cell line was investigated and compared for penetratin and pIsl, two peptides that correspond to the third helices of the related homeodomains, from the Antennapedia transcription factor of Drosophila and the rat insulin-1 gene enhancer protein, respectively. Both biotinylated peptides internalized into the cells with similar efficacy, yielding an analogous intracellular distribution. When a large cargo protein, 63 kDa avidin, was coupled to either peptide, efficient cellular uptake for both the peptide-protein complexes was observed. The interactions between each peptide and SDS micelles were studied by fluorescence spectroscopy and acrylamide quenching of the intrinsic tryptophan (Trp) fluorescence. Both peptides interacted strongly and almost identically with the membrane mimicking environment. Compared to penetratin, the new transport peptide pIsl has only one Trp residue, which simplifies the interpretation of the fluorescence spectra and in addition has a native Cys residue, which may be used for alternative coupling reactions of cargoes of different character.


Assuntos
Sistemas de Liberação de Medicamentos , Proteínas de Homeodomínio/química , Proteínas do Tecido Nervoso , Fragmentos de Peptídeos/farmacologia , Proteínas/farmacologia , Animais , Avidina/farmacologia , Transporte Biológico , Biotinilação , Proteínas de Transporte/farmacologia , Peptídeos Penetradores de Células , Drosophila , Humanos , Proteínas com Homeodomínio LIM , Micelas , Estrutura Terciária de Proteína , Ratos , Dodecilsulfato de Sódio , Espectrometria de Fluorescência , Fatores de Transcrição , Células Tumorais Cultivadas/metabolismo
17.
Plant J ; 27(5): 427-38, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11576427

RESUMO

Determinants for the recognition of a mitochondrial presequence by the mitochondrial processing peptidase (MPP) have been investigated using mutagenesis and bioinformatics approaches. All plant mitochondrial presequences with a cleavage site that was confirmed by experimental studies can be grouped into three classes. Two major classes contain an arginine residue at position -2 or -3, and the third class does not have any conserved arginines. Sequence logos revealed loosely conserved cleavage motifs for the first two classes but no significant amino acid conservation for the third class. Investigation of processing determinants for a class III precursor, Nicotiana plumbaginifolia F1beta precursor of ATP synthase (pF1beta), was performed using a series of pF1beta presequence mutants and mutant presequence peptides derived from the C-terminal portion of the presequence. Replacement of -2 Gln by Arg inhibited processing, whereas replacement of either the most proximally located -5 Arg or -15 Arg by Leu had only a low inhibitory effect. The C-terminal portion of the pF1beta presequence forms a helix-turn-helix structure. Mutations disturbing or prolonging the helical element upstream of the cleavage site inhibited processing significantly. Structural models of potato MPP and the C-terminal pF1beta presequence peptide were built by homology modelling and empirical conformational energy search methods, respectively. Molecular docking of the pF1beta presequence peptide to the MPP model suggested binding of the peptide to the negatively charged binding cleft formed by the alpha-MPP and beta-MPP subunits in close proximity to the H111XXE114H115X(116-190)E191 proteolytic active site on beta-MPP. Our results show for the first time that the amino acid at the -2 position, even if not an arginine, as well as structural properties of the C-terminal portion of the presequence are important determinants for the processing of a class III precursor by MPP.


Assuntos
Metaloendopeptidases/metabolismo , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Sinais Direcionadores de Proteínas , ATPases Translocadoras de Prótons/metabolismo , Sequência de Aminoácidos , Simulação por Computador , Sequência Conservada , Metaloendopeptidases/genética , Modelos Moleculares , Dados de Sequência Molecular , Mutagênese , Mutação Puntual , ATPases Translocadoras de Prótons/genética , Homologia de Sequência de Aminoácidos , Especificidade por Substrato , Peptidase de Processamento Mitocondrial
18.
Ann N Y Acad Sci ; 934: 241-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11460632

RESUMO

The flow and temperature fields around an inlet guide vane are determined numerically by a CFD method. Outer surface temperatures, heat transfer coefficient distributions, and static pressure distributions are presented. Three different thermal boundary conditions on the vane are analysed. The computed results are compared with experimental data. The governing equations are solved by a finite-volume method with the low Reynolds number version of the k-omega turbulence model by Wilcox implemented. It is found that the calculated results agree best with measurements if a conjugate heat transfer approach is applied and thus this wall condition is recommended for future investigations of film cooling of guide vanes and turbine blades.

19.
Biochim Biophys Acta ; 1512(1): 77-89, 2001 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-11334626

RESUMO

Certain short peptides, which are able to translocate across cell membranes with a low lytic activity, can be useful as carriers (vectors) for hydrophilic molecules. We have studied three such cell penetrating peptides: pAntp ('penetratin'), pIsl and transportan. pAntp and pIsl originate from the third helix of homeodomain proteins (Antennapedia and Isl-1, respectively). Transportan is a synthetic chimera (galanin and mastoparan). The peptides in the presence of various phospholipid vesicles (neutral and charged) and SDS micelles have been characterized by spectroscopic methods (fluorescence, EPR and CD). The dynamics of pAntp were monitored using an N-terminal spin label. In aqueous solution, the CD spectra of the three peptides show secondary structures dominated by random coil. With phospholipid vesicles, neutral as well as negatively charged, transportan gives up to 60% alpha-helix. pAntp and pIsl bind significantly only to negatively charged vesicles with an induction of around 60% beta-sheet-like secondary structure. With all three peptides, SDS micelles stabilize a high degree of alpha-helical structure. We conclude that the exact nature of any secondary structure induced by the membrane model systems is not directly correlated with the common transport property of these translocating peptides.


Assuntos
Lipossomos/química , Peptídeos/química , Fosfolipídeos/química , Proteínas de Transporte/química , Peptídeos Penetradores de Células , Dicroísmo Circular , Portadores de Fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Galanina/química , Peptídeos e Proteínas de Sinalização Intercelular , Fragmentos de Peptídeos/química , Ligação Proteica , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/química , Espectrometria de Fluorescência , Relação Estrutura-Atividade , Venenos de Vespas/química
20.
J Adv Nurs ; 32(5): 1213-23, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11115007

RESUMO

The purposes of the present study are (1) to assess the health-related quality of life (HRQOL) and the subjective health status in a sample of human immunodeficiency virus (HIV)-infected persons (2) to relate the results to different population groups and (3) to investigate the relationship of medical and demographic variables with HRQOL. A total of 72 HIV-infected men were included. They answered the Swedish health-related quality of life questionnaire and the health index. Demographic and medical data were obtained from the medical records. The data collection took place before entering a therapeutic HIV vaccine trial. The results showed a more negative impact on the HRQOL and subjective health status in the HIV-positive subjects, compared with male population groups. The dimensions of emotional well-being were most affected. When comparisons were made according to the medical and demographic variables for different subgroups within the HIV sample, differences in the physical-dimension scales were most prominent. Symptomatic HIV infection or acquired immunodeficiency syndrome (AIDS), anti-retroviral treatment, sick leave or disability pension, low income and basic education were associated with worse HRQOL and health status. In conclusion, it is of utmost importance to take into account, aspects of the patients' emotional well-being in nursing, as well as in medical care and interventions. Moreover, individualized caring programs are needed because the disruptions in HRQOL fluctuated within the HIV sample.


Assuntos
Atitude Frente a Saúde , Infecções por HIV/psicologia , Nível de Saúde , Qualidade de Vida , Adulto , Idoso , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Escolaridade , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Humanos , Renda/estatística & dados numéricos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Licença Médica , Inquéritos e Questionários , Suécia
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