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1.
J AOAC Int ; 103(5): 1366-1377, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33241384

RESUMO

A qualitative 3 min one-step assay for detecting beta-lactam, sulfonamide, and tetracycline antibiotics was validated following milk screening test guidelines developed by FDA-CVM, AOAC-RI, and IDF. The validated 90% detection levels with 95% confidence were: penicillin G 2 part per billion (ppb); amoxicillin 4 ppb; ampicillin 9 ppb; ceftiofur plus metabolites 50 ppb; cloxacillin 9 ppb; cephapirin 15 ppb; sulfadimethoxine 8 ppb; sulfamethazine 9 ppb; chlortetracycline 34 ppb; oxytetracycline 53 ppb; and tetracycline 42 ppb. Detection levels were lower than U.S. and Canadian allowable limits for milk and were consistent with most European Maximum Residue Limits. Tests of raw commingled cows' milk indicated a low positive error rate of <0.3% with no interferences demonstrated by 1.08 MM/mL somatic cells, Gram-positive or Gram-negative bacteria < 300 K/mL, freeze/thawing, or non-targeted drugs. Detection of incurred residues were similar to, or more sensitive to, fortified samples. Some cross reactivity across drug families occurred in interference studies and therefore initial positive samples should be confirmed with drug family specific screening methods. The National Conference of Interstate Milk Shipments approval as a bulk tank/tanker screening test was completed in three stages for each drug family, including a tetracycline confirmation procedure to target U.S. tolerance levels. Detection and robustness were found to be appropriate for multiple countries' regulatory requirements for screening tests. The method development, validation, and approval was intended to diversify and increase the verification tools for the control of the major antibiotic drug families used in managing cows' health and welfare.


Assuntos
Resíduos de Drogas , beta-Lactamas , Animais , Antibacterianos/análise , Canadá , Bovinos , Resíduos de Drogas/análise , Feminino , Contaminação de Alimentos/análise , Leite/química , Sulfonamidas , Tetraciclinas/análise , beta-Lactamas/análise
2.
Rev Sci Instrum ; 89(10): 10J113, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30399680

RESUMO

The lithium vapor box divertor is a concept for handling the extreme divertor heat fluxes in magnetic fusion devices. In a baffled slot divertor, plasma interacts with a dense cloud of Li vapor which radiates and cools the plasma, leading to recombination and detachment. Before testing on a tokamak, the concept should be validated: we plan to study detachment and heat redistribution by a Li vapor cloud in laboratory experiments. Mass changes and temperatures are measured to validate a direct simulation Monte Carlo model of neutral Li. The initial experiment involves a 5 cm diameter steel box containing 10 g of Li held at 650 °C as vapor flows out a wide nozzle into a similarly sized box at a lower temperature. Diagnosis is made challenging by the required material compatibility with lithium vapor. Vapor pressure is a steep function of temperature, so to validate mass flow models to within 10%, absolute temperature to within 4.5 K is required. The apparatus is designed to be used with an analytical balance to determine mass transport. Details of the apparatus and methods of temperature and mass flow measurements are presented.

3.
J Wound Care ; 24 Suppl 9: S4-S12, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26352284

RESUMO

OBJECTIVE: Negative pressure wound therapy (NPWT) has previously been shown to be effective in closing diabetic foot wounds that have undergone amputation over a 16-week period. For patients with plantar foot wounds, NPWT is a key therapy. An alternative NPWT with and without a novel soft, flexible port system needs to be evaluated for its comparable efficacy. Our objective was to show the non-inferiority of an alternative negative pressure system, and in a small subset, a novel foam dressing system. METHOD: We performed a single centre prospective study of patients with diabetes undergoing open bone resection in the foot for acutely infected wounds. Wounds were treated with NPWT/soft port technology (SPT), for 112 days or until primary closure or the wound was deemed ready for delayed primary closure. Rate of closure and quality of life were analysed. A previously published cohort was used as a control. RESULTS: Of the 30 patients initially recruited, 29 met eligibility requirements and had NPWT applied a median of 2 days postoperatively. There were seven patients (24%) who had delayed primary closure (mean=58 days) and 52% had sufficient progress to change in treatment (15/29; mean=62 days). Only one patient reached the 112-day mark without sufficient progress to be closed. The primary method of delayed primary closure was split-thickness skin graft. There was a reduction in wound area 56.3% (initial mean area=17.4cm(2) to final mean area=7.6 cm(2); p=0.001) at the end of treatment (mean=58.7 days) reduced to 4.3cm(2) a 67.2% reduction (p=0.004) at the end of study (112 days). CONCLUSION: The alternative NPWT and the soft port technology was well tolerated and effective in the population in aggregate. There was no inferiority between the two technologies. The aggregate closure or progression to be ready for closure rate of 75% at 69 days compares very favourably with previously published data for NPWT in this population of 56% at 56 days (range: 26-92 days). Both cohorts did significantly better than previously published standard of care closure rates of 39% at 77 days. DECLARATION OF INTEREST: J.C. Lantis is a paid consultant for Smith & Nephew, Acelity, Macrocure and Manukamed. This trial as supported by an institutional grant to St Luke's and Roosevelt Hospital sponsored by Smith & Nephew. The outcome of the trial had no bearing on the condition of the grant. No investigator holds an equity position in Smith & Nephew. C. Gendics is a paid consultant of Acelity.

4.
Clin Exp Immunol ; 182(3): 261-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26250153

RESUMO

T helper type 17 (Th17) cells have been shown to be pathogenic in autoimmune diseases; however, their role in type 1 diabetes (T1D) remains inconclusive. We have found that Th17 differentiation of CD4(+) T cells from BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice can be driven by interleukin (IL)-23+IL-6 to produce large amounts of IL-22, and these cells induce T1D in young NOD mice upon adoptive transfer. Conversely, polarizing these cells with transforming growth factor (TGF)-ß+IL-6 led to non-diabetogenic regulatory Th17 (Treg 17) cells that express high levels of aryl hydrocarbon receptor (AhR) and IL-10 but produced much reduced levels of IL-22. The diabetogenic potential of these Th17 subsets was assessed by adoptive transfer studies in young NOD mice and not NOD.severe combined immunodeficient (SCID) mice to prevent possible transdifferentiation of these cells in vivo. Based upon our results, we suggest that both pathogenic Th17 cells and non-pathogenic regulatory Treg 17 cells can be generated from CD4(+) T cells under appropriate polarization conditions. This may explain the contradictory role of Th17 cells in T1D. The IL-17 producing Treg 17 cells offer a novel regulatory T cell population for the modulation of autoimmunity.


Assuntos
Diferenciação Celular/imunologia , Citocinas/imunologia , Diabetes Mellitus Tipo 1/imunologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Animais , Diabetes Mellitus Tipo 1/patologia , Camundongos , Camundongos Endogâmicos NOD , Linfócitos T Reguladores/patologia , Células Th17/patologia
5.
J Wound Care ; 24 Suppl 2: S4-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25647506

RESUMO

OBJECTIVE: Lower extremity ulcers are caused by multiple disease processes and contribute to a high level of patient morbidity and health-care spending in the US. Negative pressure wound therapy (NPWT) has been used extensively for wound bed preparation. Our aim is to assess the efficacy of an affordable, low-profile single-use NPWT (single-use NPWT) on chronic lower extremity wounds that would usually be deemed too small or superficial for traditional NPWT. METHOD: A prospective pilot study was undertaken in which chronic lower extremity wounds were treated with single-use NPWT. Study visits were biweekly for primary contact dressing change, with the negative pressure unit being changed weekly. Biweekly assessments were made of wound appearance, surface area, depth, exudate amount, peri-wound skin integrity, and signs of clinical infection. Digital photography was performed at each visit. Patients with venous leg ulcers (VLUs) were treated with a 3-layer wrap. Diabetic foot ulcers (DFUs) were treated with off-loading shoes. RESULTS: The study recruited 12 patients. There were 13 wounds in total; two DFUs, two traumatic/postoperative/pressure ulcers, and nine VLUs. DFUs decreased in size on average 62%, VLUs by 32%, and traumatic/postoperative/pressure wounds by 74%. The wound appearance became more favourable and the wound depth decreased with the use of single-use NPWT. CONCLUSION: Single-use NPWT is a suitable therapy for chronic lower extremity wounds. Single-use NPWT led to a decrease in wound size and depth, an increased amount of granulation tissue, and a high level of patient satisfaction, with a low complication rate. DECLARATION OF INTEREST: This study was funded by Smith & Nephew, Hull, UK. JC Lantis is a paid consultant for KCI, Smith & Nephew, Healthpoint and Macrocure. C Gendics is a paid consultant for Macrocure and ManukaMed.

6.
Med Mycol ; 53(2): 107-18, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25550388

RESUMO

Because of the reduced toxicity associated with liposomal amphotericin B preparations, different amphotericin B liposome products have been made. In the present study, we compared the amphotericin B liposomal formulations, AmBisome(®) (AmBi) and Lambin(®) (Lbn), in uninfected and Aspergillus fumigatus infected mice, using several in vitro and in vivo toxicity and efficacy assays. The results showed that the formulations were significantly different, with Lbn 1.6-fold larger than AmBi. Lbn was also more toxic than AmBi based on the RBC potassium release assay and intravenous dosing in uninfected mice given a single 50 mg/kg dose (80% mortality for Lbn vs. 0% for AmBi). Renal tubular changes after intravenous daily dosing for 14 days were seen in uninfected mice given 5 mg/kg Lbn but not with AmBi. Survival following A. fumigatus challenge was 30% for 10 mg/kg Lbn and 60% for 10 mg/kg AmBi. When the BAL and lungs were collected 24 h after the second treatment, AmBi at 10 or 15 mg/kg or 15 mg/kg Lbn lowered the BAL fungal burden significantly vs. the controls (P ≤ 0.05), while there was no difference in lung fungal burden amongst the groups. In contrast, lung histopathology at this same early timepoint showed that AmBi was associated with markedly fewer fungal elements and less lung tissue damage than Lbn. In conclusion, given the differences in size, toxicity, and efficacy, AmBi and Lbn were not physically or functionally comparable, and these differences underscore the need for adequate testing when comparing amphotericin B liposome formulations.


Assuntos
Anfotericina B/administração & dosagem , Anfotericina B/efeitos adversos , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/efeitos dos fármacos , Administração Intravenosa , Animais , Aspergilose/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Contagem de Colônia Microbiana , Eritrócitos/efeitos dos fármacos , Feminino , Histocitoquímica , Túbulos Renais/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sobrevida , Resultado do Tratamento
7.
Rev Sci Instrum ; 85(11): 11E824, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25430389

RESUMO

A test stand for flowing liquid lithium is under construction at Princeton Plasma Physics Laboratory. As liquid lithium reacts with atmospheric gases and water, an electrical interlock system for detecting leaks and safely shutting down the apparatus has been constructed. A defense in depth strategy is taken to minimize the risk and impact of potential leaks. Each demountable joint is diagnosed with a cylindrical copper shell electrically isolated from the loop. By monitoring the electrical resistance between the pipe and the copper shell, a leak of (conductive) liquid lithium can be detected. Any resistance of less than 2 kΩ trips a relay, shutting off power to the heaters and pump. The system has been successfully tested with liquid gallium as a surrogate liquid metal. The circuit features an extensible number of channels to allow for future expansion of the loop. To ease diagnosis of faults, the status of each channel is shown with an analog front panel LED, and monitored and logged digitally by LabVIEW.

8.
J Wound Care ; 23(9): S4, S6, S8 passim, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25203401

RESUMO

OBJECTIVE: It is commonly believed that sharp surgical debridement provides adequate bacteria control for local wound beds, despite limited supporting scientific evidence. We undertook a prospective study to evaluate the reduction in planktonic bacteria pre- and post-operative debridement in critically colonised wounds. METHOD: Twelve patients, corresponding to 14 wounds, underwent debridement with either hydrodebridement or sharp steel debridement with pulse irrigation. Wound quantitative tissue cultures were taken pre- and post-debridement. There was no significant difference in wound aetiology or surface area between the two groups. RESULTS: TThe bacterial counts before debridement were 1×107 colony-forming units per gram (CFU/g) in the hydrodebridement group vs 1.4×107 CFU/g in the sharp debridement group; and 2.5×106 CFU/g (hydrodebridement) vs 7.5×105 CFU/g (sharp) after debridement (p=0.41). The total bacteria reduction was 7.5×106 CFU/g after hydrodebridement vs 1.3×107 CFU/g after sharp steel debridement (p=0.37). The mean percentage of bacteria killed from baseline was 75% by hydrodebridement and 93% killed by sharp debridement (p<0.05). CONCLUSION: Extensive operative debridement using either modality does not provide adequate immediate reduction in wound planktonic bioburden. However, all wounds appeared clinically appropriate for closure after debridement and postoperative antibacterial therapy. Postoperative antibacterial therapy may be imperative in cases of critically colonised wounds to achieve good outcomes. DECLARATION OF INTEREST: The senior author receives research grant support from Healthpoint Biotherapeutics; KCI; Manuka Honey; Smith & Nephew; Medline Ind., Macrocure; CODA. In addition the senior author is a consultant for: Smith & Nephew and KCI and medical consultant and reviewer for Macrocure. While the study as presented evaluates in part the efficacy of a commercial product from Smith & Nephew, no industry support for this study was sought or provided.


Assuntos
Extremidade Inferior/lesões , Plâncton , Adulto , Doença Crônica , Desbridamento , Feminino , Traumatismos do Pé/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
J Am Coll Clin Wound Spec ; 4(4): 74-80, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26199877

RESUMO

OBJECTIVE: An overabundance of bacteria in the chronic wound plays a significant role in the decreased ability for primary closure. One means of decreasing the bioburden in a wound is to operatively debride the wound for wound bed optimization prior to application of other therapy, such as Negative Pressure Wound Therapy (NPWT). We undertook a prospective pilot study to assess the efficacy of wound bed preparation for a standard algorithm (sharp surgical debridement followed by NPWT) versus one employing sharp surgical debridement followed by Negative Pressure Wound Therapy with Instillation (NPWTi). METHODS: Thirteen patients, corresponding to 16 chronic lower leg and foot wounds were taken to the operating room for debridement. The patients were sequentially enrolled in 2 treatment groups: the first receiving treatment with operative debridement followed by 1 week of NPWT with the instillation of quarter strength bleach solution; the other receiving a standard algorithm consisting of operative debridement and 1 week of NPWT. Quantitative cultures were taken pre-operatively after sterile preparation and draping of the wound site (POD # 0, pre-op), post-operatively once debridement was completed (POD # 0, post-op), and on post-operative day 7 after operative debridement (POD # 7, post-op). RESULTS: After operative debridement (post-operative day 0) there was a mean of 3 (±1) types of bacteria per wound. The mean CFU/gram tissue culture was statistically greater - 3.7 × 10(6) (±4 × 10(6)) in the NPWTi group, while in the standard group (NPWT) the mean was 1.8 × 10(6) (±2.36 × 10(6)) CFU/gram tissue culture (p = 0.016); at the end of therapy there was no statistical difference between the two groups (p = 0.44). Wounds treated with NPWTi had a mean of 2.6 × 10(5) (±3 × 10(5)) CFU/gram of tissue culture while wounds treated with NPWT had a mean of 2.79 × 10(6) (±3.18 × 10(6)) CFU/gram of tissue culture (p = 0.43). The mean absolute reduction in bacteria for the NPWTi group was 10.6 × 10(6) bacteria per gram of tissue while there was a mean absolute increase in bacteria for the NPWT group of 28.7 × 10(6) bacteria per gram of tissue, therefore there was a statistically significant reduction in the absolute bioburden in those wounds treated with NPWTi (p = 0.016). CONCLUSION: It has long been realized that NPWT does not make its greatest impact by bioburden reduction. Other work has demonstrated that debridement alone does not reduce wound bioburden by more than 1 Log. Wounds treated with NPWTi (in this case with quarter strength bleach instillation solution) had a statistically significant reduction in bioburden, while wounds treated with NPWT had an increase in bioburden over the 7 days.

10.
Toxicol Pathol ; 39(4): 706-10, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21558469

RESUMO

A single, solid, yellow-white thymic mass was found at necropsy of a two-year-old female cynomolgus macaque from a four-week, repeat-dose toxicity and immunogenicity study. Microscopically, the mass was multilobular and well encapsulated, surrounded by a thick connective tissue capsule, and composed of dense sheets of elongate or spindle-shaped cells and large cystic cavities separated by thick connective tissue stroma. Normal thymus was adjacent to the mass, but it was compressed. Within the mass were abundant interspersed Hassall's corpuscles; individual and small clusters of mature, small lymphocytes; scattered eosinophils; large areas of necrosis; focal mineralization; and cholesterol clefts. An interesting feature was the presence of large multinucleated giant cells, which varied widely in size and nuclear number. Immunohistochemical staining for two lymphocyte markers and two structural proteins confirmed the identity of the neoplastic spindle cells and other cellular components. There was no evidence of vascular invasion or metastasis. Features of the thymoma indicated it was a pre-existing condition and not treatment related.


Assuntos
Macaca fascicularis , Timoma/patologia , Timoma/veterinária , Neoplasias do Timo/patologia , Neoplasias do Timo/veterinária , Animais , Feminino , Imuno-Histoquímica , Timoma/imunologia , Timo/imunologia , Timo/patologia , Neoplasias do Timo/imunologia
11.
Wounds ; 23(12): 357-63, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25881260

RESUMO

 Although operative bypass is still considered the "gold stan- dard" for treating peripheral arterial disease, over the last decade en- dovascular interventions have become more popular and now represent the vast majority of peripheral arterial treatments being performed. Open bypass is associated with an unacceptable morbidity and mor- tality that is not encountered to the same extent with endovascular techniques. However, outcomes of endovascular intervention are de- pendent upon the location and nature of the lesion, as well as possibly the technologies available to treat the lesion and the experience of the interventionalist. In correctly selected patients, endovascular tech- niques should be the primary management employed for critical limb ischemia. The group of patients that would benefit from endovascular techniques continues to expand with new data constantly emerging. This article will review the current endovascular techniques currently being employed, focusing on the indication for specific intervention. .

12.
IEEE Trans Biomed Circuits Syst ; 1(2): 105-15, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23851665

RESUMO

A high-voltage (HV) integrated circuit has been demonstrated to transport fluidic droplet samples on programmable paths across the array of driving electrodes on its hydrophobically coated surface. This exciter chip is the engine for dielectrophoresis (DEP)-based micro-fluidic lab-on-a-chip systems, creating field excitations that inject and move fluidic droplets onto and about the manipulation surface. The architecture of this chip is expandable to arrays of N X N identical HV electrode driver circuits and electrodes. The exciter chip is programmable in several senses. The routes of multiple droplets may be set arbitrarily within the bounds of the electrode array. The electrode excitation waveform voltage amplitude, phase, and frequency may be adjusted based on the system configuration and the signal required to manipulate a particular fluid droplet composition. The voltage amplitude of the electrode excitation waveform can be set from the minimum logic level up to the maximum limit of the breakdown voltage of the fabrication technology. The frequency of the electrode excitation waveform can also be set independently of its voltage, up to a maximum depending upon the type of droplets that must be driven. The exciter chip can be coated and its oxide surface used as the droplet manipulation surface or it can be used with a top-mounted, enclosed fluidic chamber consisting of a variety of materials. The HV capability of the exciter chip allows the generated DEP forces to penetrate into the enclosed chamber region and an adjustable voltage amplitude can accommodate a variety of chamber floor thicknesses. This demonstration exciter chip has a 32 x 32 array of nominally 100 V electrode drivers that are individually programmable at each time point in the procedure to either of two phases: 0deg and 180deg with respect to the reference clock. For this demonstration chip, while operating the electrodes with a 100-V peak-to-peak periodic waveform, the maximum HV electrode waveform frequency is about 200 Hz; and standard 5-V CMOS logic data communication rate is variable up to 250 kHz. This HV demonstration chip is fabricated in a 130-V 1.0-mum SOI CMOS fabrication technology, dissipates a maximum of 1.87 W, and is about 10.4 mm x 8.2 mm.

13.
Acta Anaesthesiol Scand ; 45(8): 1042-4, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11576059

RESUMO

Reduction of postoperative pain is an important goal in the perioperative management of tonsillectomy patients. This is particularly the case for children, who often exhibit resistance to intramuscular or rectal administration of drugs. Peritonsillar bupivacaine infiltration, a relatively safe method of pain control, is in some centers frequently used by otolaryngologists for pain relief. We present the case of a 5-year-old girl who developed bilateral vocal cord paralysis following preoperative peritonsillar bupivacaine infiltration. After an uneventful tonsillectomy and extubation, stridor and respiratory distress developed. Bilateral vocal cord paralysis was seen on laryngoscopy. The patient was reintubated and five hours later was successfully extubated without further sequelae. Anesthesiologists and surgeons should be aware of this uncommon complication than can occur with the use of peritonsillar bupivacaine infiltration for pain control in tonsil surgery.


Assuntos
Anestésicos Locais/efeitos adversos , Bupivacaína/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Tonsilectomia , Paralisia das Pregas Vocais/induzido quimicamente , Pré-Escolar , Feminino , Humanos
15.
J Virol ; 75(9): 4117-28, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11287561

RESUMO

The CTC series of cobalt chelates display in vitro and in vivo activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). The experiments described here identify the stage in the virus life cycle where CTC-96 acts and demonstrate that the drug inhibits infection of susceptible cells. CTC-96 at 50 microg/ml has no effect on adsorption of virions to Vero cell monolayers. Penetration assays reveal that CTC-96 inhibits entry of the virus independent of gC and cellular entry receptors. This observation was supported by the failure to detect the accumulation of virus-specified proteins and alpha mRNA transcripts when CTC-96 is present at the onset of infection. Moreover, virion-associated alphaTIF does not accumulate in the nucleus of cells infected in the presence of CTC-96. CTC-96 targets the initial fusion event between the virus and the cell and also inhibits cell-to-cell spread and syncytium formation. Furthermore, CTC-96 inhibits plaque formation by varicella-zoster virus and vesicular stomatitis virus as efficiently as by HSV-1. Collectively, these experiments suggest that CTC-96 is a broad-spectrum inhibitor of infection by enveloped viruses and that it inhibits HSV-1 infection at the point of membrane fusion independent of the type of virus and cellular receptors present.


Assuntos
Antivirais/farmacologia , Cobalto/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Animais , Antivirais/química , Células CHO , Núcleo Celular/metabolismo , Chlorocebus aethiops , Cricetinae , Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Herpesvirus Humano 1/metabolismo , Herpesvirus Humano 1/fisiologia , Herpesvirus Humano 3/efeitos dos fármacos , Humanos , Estrutura Molecular , Compostos Organometálicos/química , RNA Mensageiro , Receptores Virais/metabolismo , Células Vero , Proteínas do Envelope Viral/metabolismo , Proteínas Virais/metabolismo , Replicação Viral/efeitos dos fármacos
16.
J Clin Child Psychol ; 29(2): 188-98, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10802828

RESUMO

Examined the role of attributional style in adolescent's psychological functioning. Specifically, we examined the cross-sectional correlates of attributional style, as well as the correlates of changes in attributional style over time. A sample of 841 adolescents with either maladaptive or adaptive attributional styles completed a battery of self-report measures at 2 points in time, 1 year apart. Measures assessed depressive symptoms and suicidality, cognitive functioning (self-esteem, pessimism, coping skills), and interpersonal functioning (social competence, conflict with parents, social support from family and friends). Results indicated that attributional style is associated with multiple depression-related variables. In addition, youth experienced significant changes in their attributional styles over time (from adaptive to maladaptive and vice versa). Finally, changes in attributional style were associated with changes in psychological symptoms and other psychosocial variables. Results are discussed in terms of their implications for the prevention and treatment of adolescent depression.


Assuntos
Cognição , Transtorno Depressivo/psicologia , Personalidade , Adaptação Psicológica , Adolescente , Psiquiatria do Adolescente , Estudos Transversais , Transtorno Depressivo/etiologia , Feminino , Humanos , Relações Interpessoais , Masculino , Autoimagem , Suicídio/psicologia
17.
Cancer Res ; 60(7): 1810-4, 2000 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-10766163

RESUMO

We and others have demonstrated that estrogen receptor alpha (ERalpha) and p53, two important regulatory proteins in breast cancer, bind to each other. In this report, using the glutathione S-transferase pull-down methodology, we show the ligand-independent interaction of ERalpha with the NH2-terminal region of p53, a region known to bind the p300 and human double minute-2 (hdm2) regulatory factors. Furthermore, we have demonstrated that ERalpha is capable of binding hdm2 directly. The interaction of ERalpha and p53 does not interfere with the binding between p53 and hdm2; rather, these proteins form a ternary complex. The effect of ERalpha on the p53-hdm2 regulatory loop has been examined. Our results indicate that ERalpha protects p53 from being deactivated by hdm2. It is evident from these investigations that the ligand-independent protection of p53 by ERalpha is a novel role for this protein in addition to its classic regulatory function as a ligand-inducible transcription factor. This study also describes a new mechanism of cellular regulation of p53 activity.


Assuntos
Proteínas Nucleares , Proteínas Proto-Oncogênicas/metabolismo , Receptores de Estrogênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Mama , Receptor alfa de Estrogênio , Feminino , Glutationa Transferase/genética , Células HeLa , Humanos , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-mdm2 , Proteínas Recombinantes de Fusão/metabolismo , Transfecção , Células Tumorais Cultivadas
18.
Psychosomatics ; 41(2): 140-6, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10749952

RESUMO

This study examines the hardiness dimensions of commitment, challenge, and control as resilience factors in adaptation among persons with symptomatic HIV disease and AIDS. Two hundred participants completed self-report questionnaires measuring hardiness, psychological distress, quality of life, and core personal beliefs. A series of standard multiple regression analyses revealed that high hardiness was significantly related to 1) lower psychological distress levels; 2) higher perceived quality of life in physical health, mental health, and overall functioning domains; 3) more positive personal beliefs regarding the benevolence of the world and people, self-worth, and randomness of life events; and 4) lowered belief in controllability of life events. Commitment was the hardiness factor that most frequently made a unique contribution to predicting adaptation in the regression models. Implications of these findings for understanding HIV-related adaptation and for clinical mental health intervention are considered. Future directions in HIV-related adaptation research are suggested.


Assuntos
Síndrome de Imunodeficiência Adquirida/psicologia , Adaptação Psicológica , Infecções por HIV/psicologia , Determinação da Personalidade , Papel do Doente , Adulto , Idoso , Feminino , Humanos , Controle Interno-Externo , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
19.
Biochem Biophys Res Commun ; 264(2): 359-64, 1999 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-10529369

RESUMO

Overexpression of the tumor suppressor p53 in HeLa cells leads to loss of the estradiol- and genistein-induced human estrogen receptor (ERalpha) transactivity. The coactivator p300, which binds to both ERalpha and p53, does not prevent this loss of hERalpha function. In this report we demonstrate that p53 physically binds to multiple domains of the hERalpha. This binding did not interfere with either the ERalpha dimerization or the interaction between hERalpha and its coactivator SRC-1. However, p53 did interfere with the hERalpha-ERE binding. These results may explain how p53 down-regulates the expression of some estrogen-responsive genes such as c-fos, c-jun, TPA, and bcl-2. This study supports the cross-talk between the p53 and the ERalpha signaling pathways.


Assuntos
Receptores de Estrogênio/metabolismo , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/farmacologia , Dimerização , Regulação para Baixo , Estradiol/farmacologia , Receptor alfa de Estrogênio , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Células HeLa , Histona Acetiltransferases , Humanos , Mutação , Proteínas Nucleares/farmacologia , Coativador 1 de Receptor Nuclear , Plasmídeos , Biossíntese de Proteínas/efeitos dos fármacos , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/genética , Proteínas Repressoras/genética , Elementos de Resposta , Transativadores/farmacologia , Fatores de Transcrição/farmacologia , Proteína Supressora de Tumor p53/genética
20.
Med Decis Making ; 19(3): 315-23, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10424838

RESUMO

Consumer choice research has shown that, contrary to normative theory, the introduction of an inferior alternative to an existing choice set can increase the likelihood that one of the original alternatives will be chosen. This phenomenon, the attraction effect, is relevant to physician decision making, particularly when the physician is in the role of a consumer who must make decisions about prescribing medications when a number of alternatives are available. To investigate the attraction effect in physician decision making, 40 internal medicine residents reviewed three patient cases (concerning depression, sinusitis, and vaginitis) and then chose the most appropriate medication for each patient. In some versions of the cases, two medication options were available. Other versions included a third medication (the decoy) that was inferior in every way to one of the original options (the target) but not to the other (the competitor). The results showed that addition of the "decoy" medication increased the likelihood of choosing the target medication. That is, the attraction effect does occur in physicians' decisions about medications. Physicians should be aware of this bias when evaluating or suggesting several similarly attractive medications or treatment options for the same medical condition.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Tratamento Farmacológico/psicologia , Médicos/psicologia , Adulto , Viés , Comportamento de Escolha , Transtorno Depressivo/tratamento farmacológico , Prescrições de Medicamentos , Feminino , Humanos , Medicina Interna/educação , Internato e Residência , Masculino , Sinusite/tratamento farmacológico , Vaginite/tratamento farmacológico
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