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1.
J Wound Ostomy Continence Nurs ; 49(5): 462-468, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36108230

RESUMO

PURPOSE: The purpose of this study was to examine best practices through utilization of United Ostomy Associations of America's (UOAA's) Ostomy and Continent Diversion Patient Bill of Rights (PBOR) from the perspective of patients and clinicians. DESIGN: Cross-sectional, comparative design. SUBJECTS AND SETTING: The sample comprised 412 patients with ostomies (colostomy, ileostomy, urostomy) and continent diversions (such as J-pouch) and 195 clinicians (physicians, nurses, nurse assistants) residing in the United States. All patients underwent surgery within the United States. Almost half of participants (n = 196/412; 47.6%) had surgery within 5 years of data collection. METHODS: Participants were recruited between 2019 and 2020. Patient data were collected from UOAA's national conference and affiliated ostomy support groups. Clinician data were collected at the 2019 National WOCN Society Conference and through affiliated nursing and medical professional societies. Participants completed a self-administered online or printed survey; items focused on the Ostomy and Continent Diversion PBOR and standards of ostomy care. RESULTS: Among clinicians familiar with the PBOR, 54% (n = 58/106) reported UOAA's PBOR was being used to inform ostomy care. When analyzing the full sample of both clinicians and patients, we found that less than 13% (n = 25/195) of clinicians and 5% (n = 20/412) of patients reported that all 16 of the recommended standards of care outlined in the PBOR were incorporated into ostomy care. Analysis also revealed differences between patients' and clinicians' reports of provision of 14 of the 16 PBOR components. They include a discussion on emotional impact of the ostomy surgery, instructions on troubleshooting potential difficulties with the ostomy, provision of educational materials, and providing information for ordering supplies. CONCLUSIONS: Study findings showed discrepancies between the PBOR standards of care being provided by clinicians versus the care patients reported they received. Findings also indicated variability in the consistency of delivering all components of the PBOR. We assert that further awareness and wider utilization of the PBOR in every health care setting in the United States are needed to provide best care to patients living with an ostomy.


Assuntos
Estomia , Derivação Urinária , Colostomia , Estudos Transversais , Humanos , Ileostomia/psicologia , Estados Unidos , Derivação Urinária/psicologia
2.
Ann Behav Med ; 52(10): 830-841, 2018 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-30212844

RESUMO

Background: Chronic stress plays a critical role in many of today's diseases and causes of death. Tobacco use reliably increases the likelihood of chronic disease development and premature death. In addition, habitual tobacco use elevates risk of chronic inflammatory diseases, and glucocorticoid therapy is often less effective in smokers compared with nonsmokers. Taken together, smokers may develop glucocorticoid insensitivity, thereby removing the body's greatest anti-inflammatory mechanism. Purpose: The purpose of this study was to examine glucocorticoid sensitivity among 24 smokers and 24 age-, sex-, and body mass index-matched never smokers who were clinically healthy individuals (i.e., no diagnosis or medication use for chronic diseases and normotensive). Method: Participants visited the lab after a 12 hr fast, provided a blood sample, and completed a series of psychosocial questionnaires. Smokers continued smoking ad libitum before the lab visit. Group differences in glucocorticoid sensitivity were examined using ANCOVA and repeated with linear mixed model to account for possible dependence among immune outcomes that matching participants on age, sex, and body mass index may have introduced. Results: Prior to clinical disease onset, smokers' peripheral blood mononuclear cells (PBMCs) exhibited reduced glucocorticoid sensitivity as well as a diminished inflammatory response to lipopolysaccharide compared with never smokers' PBMCs; results were identical regardless of statistical modeling used. Conclusions: Cigarette smoking, a self-initiated pharmacological chronic stressor, may provide a unique opportunity to examine early wear and tear on physiological functioning that may lead to chronic disease development. Additional research into PBMCs' intracellular changes must be examined as well as repeating this study in a larger, more heterogeneous population.


Assuntos
Fumar Cigarros/efeitos adversos , Fumar Cigarros/imunologia , Glucocorticoides/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Adulto , Doença Crônica , Feminino , Humanos , Masculino
3.
Child Care Health Dev ; 41(3): 459-66, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24865813

RESUMO

BACKGROUND: Previous research has demonstrated a relationship between prepubertal alcohol and tobacco use and delayed pubertal characteristics in girls. Although, laboratory research indicates that alcohol and tobacco use inhibits sexual maturation in male rats, human research in this area is lacking. To address this question among boys, we conducted a study to explore the association between early use of alcohol and tobacco and time to development of secondary sexual characteristics. METHODS: The study population included 3199 boys interviewed between the ages of 11 and 21. Participants reported the ages at which they first experienced body hair growth, deepening of the voice and facial hair growth. Early alcohol and tobacco use were defined as first use preceding the age of pubertal development among those reporting regular consumption patterns. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. RESULTS: Early alcohol use was associated with longer time to body hair growth (HR 0.77; 95% CI 0.69-0.87), voice changes (HR 0.72; 95% CI 0.64-0.82) and facial hair growth (HR 0.77; 95% CI 0.68-0.86), after adjusting for tobacco use and age at interview. Tobacco use was not independently associated with the puberty indicators after controlling for alcohol use and age at interview. CONCLUSIONS: Our findings are consistent with the hypothesis that alcohol may inhibit puberty onset in boys, an association that has been previously observed among young girls. Thus, alcohol may be an exposure deserving more scrutiny as a disruptor to normal pubertal development.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Puberdade Tardia/fisiopatologia , Uso de Tabaco/fisiopatologia , Adolescente , Fatores Etários , Consumo de Bebidas Alcoólicas/efeitos adversos , Criança , Estudos Transversais , Humanos , Estudos Longitudinais , Masculino , Puberdade Tardia/induzido quimicamente , Fatores de Risco , Texas , Uso de Tabaco/efeitos adversos , Adulto Jovem
4.
SAGE Open Nurs ; 8: 23779608221095315, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493541

RESUMO

Introduction: Ostomy stigma negatively impacts the health of people with an ostomy and contributes to a lower quality of life and health outcomes. Objective: To assess whether participants experience perceived stigmatizing sentiments (SS) from medical clinicians at the time of their ostomy procedure. Methods: Using a nonprobability sample of 312 persons with an ostomy, we conducted a retrospective descriptive study. We measured SS as patients' self-reports of verbal and non-verbal communication from clinicians that were perceived to be negative and may contribute to ostomy stigma. We used thematic analyses to analyze open-ended written comments. Results: Findings indicate that ostomy patients experience stigmatizing sentiments from their medical clinician before and after surgery. Sixteen percent of patients reported a SS, such as clinicians stating feelings of disgust, showing visible signs of disgust, or treating patients negatively regarding the ostomy. Conclusion: The perceived treatment that this patient cohort experienced in healthcare likely contributes to ostomy stigmatization and may impact ostomy patients' psychosocial adjustment. Future research should examine the specific consequences of perceived stigmatizing sentiments from medical clinicians.

5.
J Interpers Violence ; 36(15-16): NP8590-NP8614, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-31027448

RESUMO

Although past research documents strong linkages between adverse childhood experiences (ACEs), posttraumatic stress disorder (PTSD), and adult intimate partner violence (IPV) in the lives of women prisoners, researchers have often neglected to consider the potential mediating role of PTSD in the relationships between ACEs and adult IPV. Using data from a stratified random sample of all incarcerated women in Oklahoma (N = 334), we explore the relationships between ACEs, PTSD symptomology, and adult IPV utilizing a feminist life course theoretical framework. Results indicate that PTSD symptomology fully mediates the relationship between ACEs and adult IPV, suggesting that PTSD may be central to understanding pathways to adult IPV as well as offending and incarceration for women. Implications and suggestions for policy and future research are offered.


Assuntos
Experiências Adversas da Infância , Violência por Parceiro Íntimo , Prisioneiros , Transtornos de Estresse Pós-Traumáticos , Adulto , Feminino , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia
6.
Nat Commun ; 12(1): 5507, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535653

RESUMO

The specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.


Assuntos
Adipócitos/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Células 3T3-L1 , Adulto , Animais , Biópsia , Medula Óssea/patologia , Linhagem da Célula , Sobrevivência Celular , Humanos , Camundongos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Proteoma/metabolismo , Estresse Fisiológico , Análise de Sobrevida , Adulto Jovem
7.
J Patient Exp ; 7(4): 516-521, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33062872

RESUMO

BACKGROUND: Minimal research focuses on interactions between providers and new ostomy patients. Studies show that provider communication is important for patient health outcomes. OBJECTIVE: The purpose of this study was to investigate ostomy patients' perceptions of provider communication following surgery and whether interactions adequately prepare ostomy patients to care for their new appliance. METHOD: Using a nonprobability national sample of 381 ostomy patients, we conducted a retrospective quantitative study. We measured adequacy of provider communication from self-reports from ostomy patients. RESULTS: The results show that almost half of the sample (49%) reported receiving inadequate communication from providers. We also found a relationship between ostomy patients' educational level and their perceptions of receiving adequate communication. Notably, patients with lower educational attainment reported receiving adequate communication up to 4 times more than patients with higher educational attainment. CONCLUSION: Our results suggest that not only do ostomy patients need better communication from providers following their surgery but also patients with higher educational attainment appear to expect more information from providers than patients with lower educational attainment.

8.
J Racial Ethn Health Disparities ; 7(3): 519-527, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31845288

RESUMO

Disparities in healthcare and health outcomes between whites and non-whites continue to plague the US healthcare system. A large literature suggests that people of color face obstacles at various points in the healthcare system. This article examines one such obstacle: whether patients of color experience microaggressions from physicians during primary care medical visits. A majority of microaggression studies are qualitative and retrospective in nature. In the current study, we use a prospective approach to broaden how microaggressions are measured, as well as understand differential treatment of racial minorities within healthcare. Using data derived from audio recordings of medical visits (n = 224), we utilize a quantitative measure to examine microaggressions in the medical encounter. We find that when race status differences are present between patient and physician, patients of color are more likely to experience microaggressions from their physician. The results suggest that medical encounters differ depending on characteristics of the parties involved. These differences may not only perpetuate the differential treatment of people of color but also contribute to health disparities for people of color.


Assuntos
Agressão/psicologia , Negro ou Afro-Americano/psicologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Médicos/psicologia , Atenção Primária à Saúde/estatística & dados numéricos , Racismo/estatística & dados numéricos , População Branca/psicologia , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Médicos/estatística & dados numéricos , Estudos Prospectivos , Estudos Retrospectivos , Estados Unidos , População Branca/estatística & dados numéricos
9.
Science ; 178(4062): 749-50, 1972 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-4628343

RESUMO

Polystyrene spherules averaging 0.5 millimeter in diameter (range 0.1 to 2 millimeters) are abundant in the coastal waters of southern New England. Two types are present, a crystalline (clear) form and a white, opaque form with pigmentation resulting from a diene rubber. The spherules have bacteria on their surfaces and contain polychlorinated biphenyls, apparently absorbed from ambient seawater, in a concentration of 5 parts per million. White, opaque spherules are selectively consumed by 8 species of fish out of 14 species examined, and a chaetognath. Ingestion of the plastic may lead to intestinal blockage in smaller fish.


Assuntos
Poliestirenos/análise , Poluição Química da Água/análise , Animais , Bactérias , Connecticut , Sistema Digestório/análise , Peixes , Massachusetts , Bifenilos Policlorados/análise , Rhode Island , Espectrofotometria Infravermelho , Microbiologia da Água
10.
Health Serv Res Manag Epidemiol ; 6: 2333392819882871, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673570

RESUMO

OBJECTIVE: To examine the quality of provider communication over time considering the increasing emphasis on patient-centered care (PCC). Patient-centered care has been shown to have a positive impact on health outcomes, care experiences, quality-of-life, as well as decreased costs. Given this emphasis, we expect that provider-patient communication has improved over time. DATA SOURCE: We collected primary data by self-report surveys between summer 2017 and fall 2018. STUDY DESIGN: We use a quantitative retrospective cohort study of a national sample of 353 patients who had an ostomy surgery. DATA EXTRACTION METHOD: We measure provider communication from open-ended self-reports from patients of the number of stated inadequacies in their care. PRINCIPAL FINDINGS: Results show that the time since patients had their surgery is related to higher quality provider communication. That is, patients who had their surgery further back in time reported higher quality provider communication compared with patients who had their surgery performed more recently. CONCLUSION: Results suggest that the quality of provider communication has not improved even with an emphasis on PCC.

11.
Rev Sci Instrum ; 89(8): 083510, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30184681

RESUMO

A glass Cherenkov detector, called the Diagnostic for Areal Density (DAD), has been built and implemented at the OMEGA laser facility for measuring fusion gammas above 430 keV, from which remaining shell ⟨ρR⟩ abl can be determined. A proof-of-principle experiment is discussed, where signals from a surrogate gas Cherenkov detector are compared with reported values from the wedge range filter and charged particle spectrometer and found to correlate strongly. The design of the more compact port-based DAD diagnostic and results from the commissioning shots are then presented. Once absolutely calibrated, the DAD will be capable of reporting remaining shell ⟨ρR⟩ abl for plastic and glass capsules within minutes of a shot and with potentially higher precision than existing techniques.

12.
Am J Geriatr Pharmacother ; 5(1): 9-17, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17608243

RESUMO

BACKGROUND: Little is known about provider-patient communication regarding antidepressants in primary care settings. OBJECTIVE: The purpose of the study was to describe the extent to which veterans and their providers discuss anti-depressants during primary care visits, and to examine how patient characteristics are related to elements of this communication. METHODS: This study is a secondary analysis conducted of a data set of audiotaped clinic visits and previsit interviews with 253 adult male veterans seen in primary care. The study patients who were provided an initial antidepressant prescription or continued on an antidepressant on the day of the audiotaped visit and who had a diagnosis of depression, posttraumatic stress disorder, or bipolar disorder were included in the current analysis. Audiotapes were coded using a reliable instrument. Descriptive and bivariate statistics were calculated. RESULTS: Forty veterans (mean [SD] age, 58.9 [10.4] years) were eligible for study. Of these 40 veterans with a documented prescription for an antidepressant, 62.5% (n = 25) discussed these medications with their provider during the visits. If antidepressants were discussed, the provider initiated the discussion 68.0% (n = 17) of the time. Only 2 patients asked questions about their antidepressants. Thirty-two of the 40 veterans were continued users of anti-depressants; 8 began their antidepressant on the date of the audiotaped visit. Providers asked 15.6% of veterans (n = 5) on continued therapy how well their antidepressants were working and 6.3% of veterans (n = 2) on continued therapy about adverse effects. Among continued users of antidepressants, 18.8% (n = 6) expressed a complaint about their antidepressant and 21.9% (n = 7) of patients expressed an adherence problem. CONCLUSIONS: To detect and prevent problems with antidepressant therapy, primary care clinics should consider having nonphysician health care personnel ask patients taking antidepressant medication at least one open-ended question about how the antidepressant is working, another about possible adverse effects or barriers to use, and a third about adherence.


Assuntos
Antidepressivos/uso terapêutico , Comunicação , Pessoas Mentalmente Doentes , Relações Profissional-Paciente , Veteranos/psicologia , Adulto , Idoso , Antidepressivos/efeitos adversos , Transtorno Bipolar/tratamento farmacológico , Coleta de Dados , Depressão/tratamento farmacológico , Feminino , Humanos , Masculino , Serviços de Saúde Mental , Pessoa de Meia-Idade , Cooperação do Paciente , Educação de Pacientes como Assunto , Participação do Paciente , Satisfação do Paciente , Atenção Primária à Saúde , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Gravação em Fita , Estados Unidos
13.
MedGenMed ; 9(4): 48, 2007 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-18311398

RESUMO

CONTEXT: Although physician influence can be especially powerful with older adults, relatively little is known about how primary care physicians (PCPs) interact with their patients regarding lifestyle issues. OBJECTIVE: To document the length of time that PCPs discuss lifestyle issues with their older patients and to examine patient, physician, and contextual correlates. DESIGN: Descriptive and multivariate analysis of videotapes of physician-patient encounters. SETTING: Medical encounters from 3 primary care ambulatory settings. PATIENTS: There were 116 ongoing medical encounters with patients aged 65 years or older. MAIN OUTCOME MEASURES: Total time spent in physical activity (PA) discussions and total time spent discussing PA, nutrition, and smoking during the medical encounter. RESULTS: Very little time was spent in lifestyle discussions. On average, PA was discussed for less than a minute (58.28 seconds) and nutrition for slightly less than 90 seconds (83.11 seconds). Only about 10% of the average 17-minute, 22-second encounter was spent on physical activity, nutrition, or smoking topics. Physician supportiveness score (beta = 8.92, P

Assuntos
Assistência Ambulatorial/normas , Atitude do Pessoal de Saúde , Estilo de Vida , Relações Médico-Paciente , Atenção Primária à Saúde/métodos , Idoso , Assistência Ambulatorial/tendências , Feminino , Avaliação Geriátrica , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Análise Multivariada , Avaliação das Necessidades , Médicos de Família , Probabilidade , Qualidade da Assistência à Saúde , Fatores de Tempo , Gravação em Vídeo
14.
Nucleic Acids Res ; 27(16): 3325-33, 1999 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-10454640

RESUMO

From a sarkosyl-insoluble outer membrane fraction prepared from the Helicobacter pylori strain ATCC 43504, 19 proteins could be sequenced N-terminally by Edman degradation. Oligonucleotides were deduced and used for screening of a genomic library. From the isolated genes, five code for different members of a H.pylori outer membrane protein (Hop) family. Among these, the hopZ gene was characterized in more detail. It encodes a protein which was shown to be located at the bacterial surface by immunofluorescence studies. Sequence analysis of the hopZ gene from 15 different H.pylori strains revealed the existence of two alleles and the possible regulation of hopZ expression by slipped-strand mispairing within a CT dinucleotide repeat motif located in the signal-peptide coding region. Among the different strains, the influence of this region on the expression of HopZ was analyzed on a translational level by western blot analysis of bacterial extracts and immunofluorescence studies on intact cells. The protein is expressed only in those strains in which the number of the CT dinucleotide repeats allow for an open reading frame encoding the complete protein. Addionally the function of HopZ was investigated in an adhesion assay. The wild-type strain ATCC 43504 adhered to human gastric epithel cells whereas a knockout mutant strain showed significantly reduced binding to the cells.


Assuntos
Aderência Bacteriana/genética , Proteínas da Membrana Bacteriana Externa/genética , Helicobacter pylori/fisiologia , Alelos , Sequência de Aminoácidos , Proteínas da Membrana Bacteriana Externa/fisiologia , Sequência de Bases , Clonagem Molecular , Primers do DNA , Mucosa Gástrica/microbiologia , Variação Genética , Genótipo , Humanos , Dados de Sequência Molecular , Homologia de Sequência de Aminoácidos
15.
J Healthc Manag ; 50(5): 297-309; discussion 309-10, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16268409

RESUMO

Studies of disease management (DM) have shown that patients who participate in such programs achieve better health status and make fewer emergency room visits. Private and government payers have recently increased their efforts to promote DM initiatives through financial incentives to healthcare providers. This article explores opportunities for administrators of health services organizations (HSO) to promote DM in the current political and economic environment. Our survey of professionals (DM leaders, physicians, and DM nurses) in six DM programs reveals these professionals' assessments of the key players and resources that they deem important to their respective DM programs. They view DM programs as heavily dependent on the support of physicians, nurses, and health plan leaders but relatively less so on the support of HSO administrators- a situation that may suggest opportunities for administrators to take on greater leadership in moving the HSO toward developing DM programs. Survey results also indicate a strong need for the integration of resources such as communication systems, electronic medical records, and DM reporting. Taken collectively, these needs suggest a number of strategies for the administrator to play a larger role in supporting the adoption and effective implementation of DM. In the article, we propose that DM programs can benefit substantially from an administrator who can demonstrate a thorough knowledge of DM-related government and private-payer initiatives and who has the ability to provide leadership to develop and implement viable DM programs. Valued contributions that the administrator should bring to the table include support of standardized DM processes, use of practice guidelines, and provision of pertinent information systems.


Assuntos
Pessoal Administrativo , Atitude do Pessoal de Saúde , Gerenciamento Clínico , Liderança , Desenvolvimento de Programas , Centers for Medicare and Medicaid Services, U.S. , Coleta de Dados , Difusão de Inovações , Eficiência Organizacional , Humanos , Enfermeiras e Enfermeiros/psicologia , Médicos/psicologia , Técnicas de Planejamento , Reembolso de Incentivo , Estados Unidos
16.
Oncogene ; 34(40): 5128-40, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25619842

RESUMO

Oxygen and nutrient limitation are common features of the tumor microenvironment and are associated with cancer progression and induction of metastasis. The inefficient vascularization of tumor tissue also limits the penetration of other serum-derived factors, such as lipids and lipoproteins, which can be rate limiting for cell proliferation and survival. Here we have investigated the effect of hypoxia and serum deprivation on sterol regulatory element-binding protein (SREBP) activity and the expression of lipid metabolism genes in human glioblastoma multiforme (GBM) cancer cells. We found that SREBP transcriptional activity was induced by serum depletion both in normoxic and hypoxic cells and that activation of SREBP was required to maintain the expression of fatty acid and cholesterol metabolism genes under hypoxic conditions. Moreover, expression of stearoyl-CoA desaturase, the enzyme required for the generation of mono-unsaturated fatty acids, and fatty acid-binding protein 7, a regulator of glioma stem cell function, was strongly dependent on SREBP function. Inhibition of SREBP function blocked lipid biosynthesis in hypoxic cancer cells and impaired cell survival under hypoxia and in a three-dimensional spheroid model. Finally, gene expression analysis revealed that SREBP defines a gene signature that is associated with poor survival in glioblastoma.


Assuntos
Neoplasias Encefálicas/patologia , Sobrevivência Celular/fisiologia , Glioblastoma/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Hipóxia Celular/fisiologia , Linhagem Celular , Glioblastoma/metabolismo , Glioblastoma/mortalidade , Humanos , Imuno-Histoquímica , Metabolismo dos Lipídeos/fisiologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase , Modelos de Riscos Proporcionais , RNA Interferente Pequeno , Transcriptoma , Transfecção
17.
Hum Gene Ther ; 10(12): 1953-64, 1999 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-10466629

RESUMO

We conducted a phase I hematopoietic stem cell (HSC) gene-marking trial in patients undergoing autologous blood or marrow stem cell transplant for the treatment of multiple myeloma. Between 500 and 1000 ml of bone marrow was harvested from each of 14 myeloma patients and 1 syngeneic donor. A mean of 3.3x10(9) cells per patient were plated in 20 to 50 long-term marrow culture (LTMC) flasks and maintained for 3 weeks. LTMCs were exposed on days 8 and 15 to clinical-grade neo(r)-containing retrovirus supernatant (G1Na). A mean of 8.23x10(8) day-21 LTMC cells containing 5.2x10(4) gene-marked granulocyte-macrophage progenitor cells (CFU-GM) were infused along with an unmanipulated peripheral blood stem cell graft into each patient after myeloablative therapy. Proviral DNA was detected in 71% of 68 tested blood and bone marrow samples and 150 of 2936 (5.1%) CFU-GM derived from patient bone marrow samples after transplant. The proportion of proviral DNA-positive CFU-GM declined from a mean of 9.8% at 3 months to a mean of 2.3% at 24 months postinfusion. Southern blots of 26 marrow and blood samples were negative. Semiquantitative PCR analysis indicated that gene transfer was achieved in 0.01-1% of total bone marrow and blood mononuclear cells (MNCs). Proviral DNA was also observed in EBV-transformed B lymphocytes, in CD34+ -enriched bone marrow cells, and in CFUs derived from the latter progenitors. Gene-modified cells were detected by PCR in peripheral blood and bone marrow for 24 months after infusion of LTMC cells. Sensitivity and specificity of the PCR assays were independently validated in four laboratories. Our data confirm that HSCs may be successfully transduced in stromal based culture systems. The major obstacle to therapeutic application of this approach remains the overall low level of genetically modified cells among the total hematopoietic cell pool in vivo.


Assuntos
Transplante de Medula Óssea , Técnicas de Transferência de Genes , Marcadores Genéticos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/fisiologia , Mieloma Múltiplo/terapia , Células da Medula Óssea/patologia , Células da Medula Óssea/fisiologia , Células Cultivadas , DNA Viral/análise , Vetores Genéticos , Células-Tronco Hematopoéticas/patologia , Humanos , Canamicina Quinase/genética , Reação em Cadeia da Polimerase/métodos , Provírus , Retroviridae/genética , Transplante Autólogo
18.
Microbes Infect ; 3(3): 171-9, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11358711

RESUMO

In search of protective antigens which can be used in a vaccine to prevent Helicobacter pylori infection, we report on the identification of four genes, hopV, hopW, hopX and hopY, and the characterization of the corresponding proteins which belong to the H. pylori outer membrane protein (Hop) family containing 32 homologous members, some of which were shown to function as porins. Sequence analysis of 16 different H. pylori strains revealed that the proteins HopV, HopW, HopX and HopY are highly conserved. Localization of HopV, HopW, HopX and HopY at the surface of the bacteria was investigated by immunofluorescence. Using a planar lipid bilayer system the proteins HopV and HopX were shown to form pores with single-channel conductances of 1.4 and 3.0 nS, respectively.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Helicobacter pylori/genética , Sequência de Aminoácidos , Animais , Proteínas da Membrana Bacteriana Externa/biossíntese , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/imunologia , Western Blotting , Imunofluorescência , Helicobacter pylori/química , Helicobacter pylori/imunologia , Soros Imunes , Dados de Sequência Molecular , Porinas/química , Porinas/imunologia , Coelhos , Proteínas Recombinantes/imunologia , Alinhamento de Sequência
19.
Brain Res ; 568(1-2): 244-52, 1991 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-1839967

RESUMO

In chronically prepared rats, electrical stimulation (100 Hz, 0.1 ms pulses) of the dorsal raphe nucleus, some sites in the median raphe nucleus, and adjoining regions of the midbrain produced locomotion accompanied by hippocampal rhythmical slow activity (RSA) and neocortical low voltage fast activity (LVFA). Both the behaviour and the cerebral waveforms persisted after injection of scopolamine HBr (5 mg/kg, s.c.). Median raphe stimulation usually produced behavioural freezing or an unnatural forced movement accompanied by RSA and LVFA. The behavioural response and the LVFA were not affected by scopolamine but scopolamine eliminated the RSA, replacing it with a low amplitude irregular (suppressed) pattern. p-Chlorophenylalanine (PCPA, 500 mg/kg/day x 3, i.p.) reduced the RSA and LVFA normally present during walking after scopolamine but did not reduce the hippocampal suppression produced by median raphe stimulation in scopolamine-treated rats. Hippocampal suppression and LVFA in response to median raphe stimulation were also present in urethane (1.0-1.5 g/kg, i.p.) anesthetized rats, whether pretreated with PCPA or not. Stimulation at most other midbrain sites produced RSA and LVFA in the urethane condition. RSA was abolished in the urethane plus scopolamine condition. The data support the view that scopolamine-resistant RSA and LVFA are dependent on serotonergic projections. The hippocampal suppression produced by median raphe stimulation may be dependent on non-serotonergic neurotransmission.


Assuntos
Comportamento Animal/fisiologia , Córtex Cerebral/fisiologia , Hipocampo/fisiologia , Núcleos da Rafe/fisiologia , Animais , Atropina/farmacologia , Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Estimulação Elétrica , Eletrofisiologia/métodos , Fenclonina/farmacologia , Masculino , Mesencéfalo/fisiologia , Atividade Motora/efeitos dos fármacos , Movimento , Especificidade de Órgãos , Ratos , Valores de Referência , Escopolamina/farmacologia , Uretana/farmacologia
20.
Chemosphere ; 40(9-11): 1179-87, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10739060

RESUMO

Recent monitoring data indicate that portions of Italy's Venice Lagoon ecosystem have been degraded due to biological and chemical pollution from a variety of potential sources. Using polychlorinated dibenzo-p-dioxin (PCDD) and dibenzofuran (PCDF) data collected from sediment, fish and shellfish in the Lagoon, a screening-level ecological risk assessment (ERA) was performed to evaluate the risks to representative aquatic biota and wildlife receptors. Risks to aquatic invertebrates posed by PCDD/Fs in sediment were evaluated by comparing measured tissue concentrations in fish and shellfish to appropriate ecotoxicological reference values. For mammalian and avian receptors, risks posed by theoretical exposures to PCDD/Fs through the food chain were calculated using conservative wildlife exposure models. Results of the screening-level approach indicate that the potential for adverse effects to fish and aquatic invertebrate receptors from PCDD/Fs in surficial sediments are unlikely. Adverse effects to wildlife are possible but highly uncertain, and warrants further investigation in a more comprehensive ERA.


Assuntos
Benzofuranos/análise , Dibenzodioxinas Policloradas/análogos & derivados , Poluentes do Solo/análise , Poluentes da Água/análise , Animais , Dibenzofuranos Policlorados , Ecologia , Peixes , Cadeia Alimentar , Itália , Dibenzodioxinas Policloradas/análise , Medição de Risco , Frutos do Mar/análise
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