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1.
eNeurologicalSci ; : 100349, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34151034

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread as a global pandemic with significant morbidity and mortality. As the prevalence of COVID-19 has risen, so has the diversity of its clinical presentation. SARS-CoV-2 is considered to have neuroinvasive and neurotropic qualities that can lead to central and peripheral nervous system manifestations. We describe a 65-year-old woman who developed new-onset unilateral ptosis and mitosis following a diagnosis of COVID-19. To our knowledge, this is the first reported case describing transient Horner syndrome in association with COVID-19.

2.
Neurourol Urodyn ; 40(2): 653-658, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33348425

RESUMO

AIMS: This study aimed to evaluate the initial efficacy, safety, and usability of a novel, dynamic, and disposable intravaginal device in women suffering from stress urinary incontinence (SUI). METHODS: Twenty-six women with SUI were recruited to perform a modified 1-h Pad Weight Gain (PWG) test. In this test, women drank 250-500 ml of water, were given a pre-weighed pad, and asked to perform a set of incontinence-inducing activities. At the end of the activities session, the pad was removed and weighed. This test was performed both with and without the Nolix device. Three efficacy endpoints measured were continuous percent reduction in urine leakage, dryness (defined as pad weight increase by no more than 1 g), and improvement in pad weight (measured as continuous percent reduction in PWG ≥ 50%). Any adverse events, reported by subjects during the device use were recorded. The usability and user's satisfaction were assessed using the Benefit, Satisfaction, and Willingness to Continue and Nolix Satisfaction questionnaires. RESULTS: The average reduction in PWG was 79.4%. The average reduction in urine leakage while using the device was at least 70%. In addition, in 79.5% of tests, the clinically meaningful level of improvement in PWG was achieved. Use of the device produced substantial improvement in the patient's perceived quality of life. No adverse events were reported during the study. CONCLUSION: The Nolix device served as a noninvasive, effective, and well-tolerated treatment option for reducing SUI in a modified 1-h PWG test with a set of incontinence-inducing activities.


Assuntos
Medicamentos sem Prescrição/uso terapêutico , Incontinência Urinária por Estresse/tratamento farmacológico , Estudos Cross-Over , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
3.
Clin Anat ; 33(2): 293-299, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31749197

RESUMO

Few neuroimaging anatomic studies to date have investigated in detail the point of entry of cortical bridging veins (CBVs) into the superior sagittal sinus (SSS). Although we know that most CBVs join the SSS at an acute angle opposite to the direction of SSS blood flow, the three-dimensional (3-D) spatial configuration of these venous confluences has not been studied previously. This anatomical information would be pertinent to several clinically applicable scenarios, such as in planning intracranial surgical approaches that preserve bridging veins; studying anatomical factors in the pathophysiology of SSS thrombosis; and when planning endovascular microcatheterization of pial veins to retrogradely embolize brain arteriovenous malformations (AVMs). We used the concept of Euclidean planes in 3-D space to calculate the arccosine of these CBV-SSS angles of confluence. To test the hypothesis that pial AVM draining veins may not be any more acutely angled or difficult to microcatheterize at the SSS than for normal CBVs, we measured 70 angles of confluence on magnetic resonance venography images of 11 normal, and nine AVM patients. There was no statistical difference between normal and AVM patients in the CBV-SSS angles projected in 3-D space (56.2° [SD = 22.4°], and 46.2° [SD = 22.3°], respectively; P > 0.05). Hence, participation of CBVs in drainage of pial AVMs should not confer any added difficulty to their microcatheterization across the SSS, when compared to the acute angles found in normal individuals. This has useful implications for potential choices of strategies requiring endovascular transvenous retrograde approaches to treat AVMs. Clin. Anat. 33:293-299, 2020. © 2019 Wiley Periodicals, Inc.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Seio Sagital Superior/diagnóstico por imagem , Adolescente , Adulto , Idoso , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
4.
Front Physiol ; 10: 1250, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31607956

RESUMO

There are currently no in vivo techniques to accurately study dynamic equilibrium of blood flow within separate regions (compartments) of a large brain arteriovenous malformation (AVM) nidus. A greater understanding of this AVM compartmentalization, even if theoretical, would be useful for optimal planning of endovascular and multimodal AVM therapies. We aimed to develop a biomathematical AVM model for theoretical investigations of intranidal regions of increased mean intravascular pressure (Pmean) and flow representing hemodynamic compartments, upon simulated AVM superselective angiography (SSA). We constructed an AVM model as a theoretical electrical circuit containing four arterial feeders (AF1-AF4) and a three-dimensional nidus of 97 interconnected plexiform and fistulous components. We simulated SSA by increases in Pmean in each AF (with and without occlusion of all other AFs), and then used network analysis to establish resulting increases in Pmean and flow within each nidus vessel. We analyzed shifts in hemodynamic compartments consequent to increasing AF injection pressures. SSA simulated by increases of 10 mm Hg in AF1, AF2, AF3, or AF4 resulted in dissipation of Pmean over 38, 66, 76, or 20% of the nidus, respectively, rising slightly with simultaneous occlusion of other AFs. We qualitatively analyzed shifting intranidal compartments consequent to varying injection pressures by mapping the hemodynamic changes onto the nidus network. Differences in extent of nidus filling upon SSA injections provide theoretical evidence that hemodynamic and angioarchitectural features help establish AVM nidus compartmentalization. This model based on a theoretical AVM will serve as a useful computational tool for further investigations of AVM embolotherapy strategies.

5.
Comput Biol Med ; 113: 103416, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31494430

RESUMO

BACKGROUND: Theoretical modeling allows investigations of cerebral arteriovenous malformation (AVM) hemodynamics, but current models are too simple and not clinically representative. We developed a more realistic AVM model based on graphics processing unit (GPU) computing, to replicate highly variable and complex nidus angioarchitectures with vessel counts in the thousands-orders of magnitude greater than current models. METHODS: We constructed a theoretical electrical circuit AVM model with a nidus described by a stochastic block model (SBM) of 57 nodes and an average of 1000 plexiform and fistulous vessels. We sampled and individually simulated 10,000 distinct nidus morphologies from this SBM, constituting an ensemble simulation. We assigned appropriate biophysical values to all model vessels, and known values of mean intravascular pressure (Pmean) to extranidal vessels. We then used network analysis to calculate Pmean and volumetric flow rate within each nidus vessel, and mapped these values onto a graphic representation of the nidus network. We derived an expression for nidus rupture risk and conducted a model parameter sensitivity analysis. RESULTS: Simulations revealed a total intranidal volumetric blood flow ranging from 268 mL/min to 535 mL/min, with an average of 463 mL/min. The maximum percentage rupture risk among all vessels in the nidus ranged from 0% to 60%, with an average of 29%. CONCLUSION: This easy to implement biomathematical AVM model, allowed by parallel data processing using advanced GPU computing, will serve as a useful tool for theoretical investigations of AVM therapies and their hemodynamic sequelae.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Simulação por Computador , Hemodinâmica , Malformações Arteriovenosas Intracranianas/fisiopatologia , Modelos Cardiovasculares , Feminino , Humanos , Masculino
6.
Clin Anat ; 32(5): 618-629, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30807670

RESUMO

A high lumbar puncture (LP) at L2-L3 or above is often necessary to consider on technical grounds, but complications of conus medullaris (CM) damage during high LP are potentially concerning. We hypothesized that a high LP might be safer than previously thought by accounting for movements of the CM upon patient positional changes. We retrospectively reviewed standard normal supine lumbar spine magnetic resonance imaging of 58 patients and used electronic calipers on axial images at the T12-L1, L1-L2, and L2-L3 disc levels to measure the transverse diameter of the CM relative to the size of the dorsal thecal sac space (DTSS) through which a spinal needle could be inserted. On 142 axial images, the means for CM diameters were 8.2, 6.0, and 2.9 mm at the three levels, respectively. We then used known literature mean CM displacement values in the legs flexed and unflexed lateral decubitus position (LDP) to factor in CM shifts to the dependent side. We found that at all three levels, the likely positional shift of the CM would be too small and insufficient to displace the entire CM out of the DTSS. However, if needle placement could be confined to the midsagittal plane, an LP in the unflexed LDP would theoretically be entirely safe at both L1-L2 and L2-L3, and almost so at L2-L3 in the legs flexed LDP. Thus, high LPs at L1-L2 and L2-L3 are in theory likely safer than considered previously, more so in the legs unflexed than in the flexed LDP. Clin. Anat. 32:618-629, 2019. © 2019 Wiley Periodicals, Inc.


Assuntos
Vértebras Lombares/anatomia & histologia , Medula Espinal/anatomia & histologia , Punção Espinal/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cauda Equina/anatomia & histologia , Cauda Equina/diagnóstico por imagem , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medula Espinal/diagnóstico por imagem , Decúbito Dorsal , Adulto Jovem
7.
Int Urogynecol J ; 27(2): 233-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26282093

RESUMO

INTRODUCTION AND HYPOTHESIS: For the surgical correction of apical prolapse the abdominal approach is associated with better outcomes; however, it is more expensive than the transvaginal approach. This cost-effectiveness analysis compares abdominal sacral colpopexy (ASC) with sacrospinous ligament fixation (SSLF) to determine if the improved outcomes of ASC justify the increased expense. METHODS: A decision-analytic model was created comparing ASC with SSLF using data-modeling software, TreeAge Pro (2013), which included the following outcomes: post-operative stress urinary incontinence (SUI) with possible mid-urethral sling (MUS) placement, prolapse recurrence with possible re-operation, and post-operative dyspareunia. Cost-effectiveness was defined as an incremental cost-effectiveness ratio (ICER) of less than $50,000 per quality-associated life year (QALY). Base-case, threshold, and one-way sensitivity analyses were performed. RESULTS: At the baseline, ASC is more expensive than SSLF ($13,988 vs $11,950), but is more effective (QALY 1.53 vs 1.45) and is cost-effective (ICER $24,574/QALY) at 2 years. ASC was not cost-effective if the following four thresholds were met: the rate of post-operative SUI was above 36 % after ASC or below 28 % after SSLF; the rate of MUS placement for post-operative SUI was above 60 % after ASC or below 13 % after SSLF; the rate of recurrent prolapse was above 15 % after ASC or below 4 % after SSLF; the rate of post-operative dyspareunia was above 59 % after ASC or below 19 % after SSLF. CONCLUSIONS: Abdominal sacral colpopexy can be cost-effective compared with sacrospinous ligament fixation; however, as the post-operative outcomes of SSLF improve, SSLF can be considered a cost-effective alternative.


Assuntos
Técnicas de Apoio para a Decisão , Procedimentos Cirúrgicos em Ginecologia/economia , Prolapso de Órgão Pélvico/cirurgia , Análise Custo-Benefício , Dispareunia/etiologia , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Ligamentos/cirurgia , Prolapso de Órgão Pélvico/economia , Anos de Vida Ajustados por Qualidade de Vida , Recidiva , Slings Suburetrais/efeitos adversos , Slings Suburetrais/economia , Incontinência Urinária por Estresse/etiologia , Vagina/cirurgia
8.
Fertil Steril ; 103(5): 1215-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25772770

RESUMO

OBJECTIVE: To determine whether in vitro fertilization with preimplantation genetic screening (IVF/PGS) is cost effective compared with expectant management in achieving live birth for patients with unexplained recurrent pregnancy loss (RPL). DESIGN: Decision analytic model comparing costs and clinical outcomes. SETTING: Academic recurrent pregnancy loss programs. PATIENT(S): Women with unexplained RPL. INTERVENTION(S): IVF/PGS with 24-chromosome screening and expectant management. MAIN OUTCOMES MEASURE(S): Cost per live birth. RESULT(S): The IVF/PGS strategy had a live-birth rate of 53% and a clinical miscarriage rate of 7%. Expectant management had a live-birth rate of 67% and clinical miscarriage rate of 24%. The IVF/PGS strategy was 100-fold more expensive, costing $45,300 per live birth compared with $418 per live birth with expectant management. CONCLUSION(S): In this model, IVF/PGS was not a cost-effective strategy for increasing live birth. Furthermore, the live-birth rate with IVF/PGS needs to be 91% to be cost effective compared with expectant management.


Assuntos
Aborto Habitual/economia , Aborto Habitual/prevenção & controle , Análise Custo-Benefício , Fertilização In Vitro/economia , Testes Genéticos/economia , Custos de Cuidados de Saúde , Diagnóstico Pré-Implantação/economia , Aborto Habitual/diagnóstico , Aborto Habitual/genética , Técnicas de Apoio para a Decisão , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Nascido Vivo , Modelos Econômicos , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Implantação/métodos , Resultado do Tratamento
9.
Am J Obstet Gynecol ; 207(4): 326.e1-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22840972

RESUMO

OBJECTIVE: This study investigates the cost effectiveness of gestational diabetes mellitus screening using the new International Association of Diabetes in Pregnancy Study Group (IADPSG) guidelines. STUDY DESIGN: A decision analytic model was built comparing routine screening with the 2-hour (2h) oral glucose tolerance test (OGTT) vs the 1-hour glucose challenge test. All probabilities, costs, and benefits were derived from the literature. Base case, sensitivity analyses, and a Monte Carlo simulation were performed. RESULTS: Screening with the 2h OGTT was more expensive, more effective, and cost effective at $61,503/quality-adjusted life year. In a 1-way sensitivity analysis, the more inclusive IADPSG diagnostic approach remained cost effective as long as an additional 2.0% or more of patients were diagnosed and treated for gestational diabetes mellitus. CONCLUSION: Screening at 24-28 weeks' gestational age under the new IADPSG guidelines with the 2h OGTT is expensive but cost effective in improving maternal and neonatal outcomes. How the health care system will provide expanded care to this group of women will need to be examined.


Assuntos
Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose/economia , Guias de Prática Clínica como Assunto , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Diabetes Gestacional/economia , Feminino , Humanos , Gravidez , Anos de Vida Ajustados por Qualidade de Vida
10.
Am J Obstet Gynecol ; 205(3): 282.e1-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22071065

RESUMO

OBJECTIVE: This study investigated the cost-effectiveness of treating mild gestational diabetes mellitus (GDM). STUDY DESIGN: A decision analytic model was built to compare treating vs not treating mild GDM. The primary outcome was the incremental cost per quality-adjusted life year (QALY). All probabilities, costs, and benefits were derived from the literature. Base case, sensitivity analyses, and a Monte Carlo simulation were performed. RESULTS: Treating mild GDM was more expensive, more effective, and cost-effective at $20,412 per QALY. Treatment remained cost-effective when the incremental cost to treat GDM was less than $3555 or if treatment met at least 49% of its reported efficacy at the baseline cost to treat of $1786. CONCLUSION: Treating mild GDM is cost-effective in terms of improving maternal and neonatal outcomes including decreased rates of preeclampsia, cesarean sections, macrosomia, shoulder dystocia, permanent and transient brachial plexus injury, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal intensive care unit admissions.


Assuntos
Diabetes Gestacional/economia , Custos de Cuidados de Saúde , Adulto , Cesárea/economia , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Diabetes Gestacional/tratamento farmacológico , Distocia/economia , Feminino , Humanos , Gravidez , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença
11.
Environ Technol ; 29(10): 1075-84, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18942575

RESUMO

The electro-dewatering method is regarded as a promising approach to reduce the water content in sludge. Laboratory scale non-pressure and pressure-driven dewatering reactors were set up to study the dewatering rate in different types of sludge and the water content in the final sludge cake after electro-dewatering process. It was observed that in non-pressure experiments, the water removal rate was highly dependent on sludge pH buffering capacity and the type of sludge; the highest water removal rate (83.2 lm(-2) day(-1)) was achieved with anaerobic sludge. When pressure was applied, the rate of removal of water from the anode and the cathode depended on alkalinity as well as current density. During the electro-dewatering process, pressure had a significant contribution to water reduction in the final sludge cake in experiments using raw sludge and raw sludge with added alkalinity in comparison with non-pressure experiments using the same types of sludge. However, experiments using anaerobically digested sludge in non-pressure and pressure-driven reactors resulted in the same water content in the final sludge cake (40%). In general, different types of sludge with various amounts of alkalinity affected sludge electro-dewatering capacity by changing zeta potential and pH. Migration of negatively charged organic substances occurred during the applied low-level direct current (15 V), and chemical oxygen demand and total organic carbon concentrations in removed water were found to be higher at the anode and lower at the cathode in comparison with control experiments.


Assuntos
Esgotos/química , Eliminação de Resíduos Líquidos/métodos , Anaerobiose , Eletroquímica , Concentração de Íons de Hidrogênio , Pressão , Esgotos/microbiologia
12.
West Indian Med J ; 56(1): 5-10, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17621837

RESUMO

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24% and 50.83% anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.


Assuntos
Furanos/farmacologia , Myoporaceae , Neuroblastoma/tratamento farmacológico , Pentanonas/farmacologia , Fitoterapia , Sarcoma/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Humanos , Pentanonas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta , Caules de Planta
13.
West Indian med. j ; 56(1): 5-10, Jan. 2007.
Artigo em Inglês | LILACS | ID: lil-471845

RESUMO

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24and 50.83anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.


Assuntos
Humanos , Furanos/farmacologia , Myoporaceae , Neuroblastoma/tratamento farmacológico , Fitoterapia , Pentanonas/farmacologia , Sarcoma/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular , Ensaios de Seleção de Medicamentos Antitumorais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Furanos/química , Folhas de Planta , Caules de Planta , Pentanonas/química , Proliferação de Células/efeitos dos fármacos
14.
Fitoterapia ; 75(2): 117-22, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15030914

RESUMO

The phytochemical investigation of the aerial parts of Tribulus terrestris of Bulgarian origin has resulted in the isolation of the novel furostanol saponin 1, named tribol, together with the known spirostanol saponins 2 and 3 and sitosterol glucoside. The structure of tribol was determined as (25R)-furost-5(6)-ene-3beta,16,26-triol-3-O-alpha-rhamnopyranosyl-(1-->2)-[alpha-rhamnopyranosyl-(1-->4)]-beta-glucopyranoside (1) by spectral analysis, including extensive 1D and 2D-NMR experiments.


Assuntos
Fitoterapia , Extratos Vegetais/química , Tribulus , Bulgária , Humanos , Espectroscopia de Ressonância Magnética , Medicina Tradicional , Componentes Aéreos da Planta , Saponinas/química
15.
J Virol ; 76(15): 7760-76, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12097589

RESUMO

We describe the further properties of a protein, designated SOS gp140, wherein the association of the gp120 and gp41 subunits of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein is stabilized by an intersubunit disulfide bond. HIV-1(JR-FL) SOS gp140, proteolytically uncleaved gp140 (gp140(UNC)), and gp120 were expressed in stably transfected Chinese hamster ovary cells and analyzed for antigenic and structural properties before and after purification. Compared with gp140(UNC), SOS gp140 reacted more strongly in surface plasmon resonance and radioimmunoprecipitation assays with the neutralizing monoclonal antibodies (MAbs) 2G12 (anti-gp120), 2F5 (anti-gp41), and 17b (to a CD4-induced epitope that overlaps the CCR5-binding site). In contrast, gp140(UNC) displayed the greater reactivity with nonneutralizing anti-gp120 and anti-gp41 MAbs. Immunoelectron microscopy studies suggested a model for SOS gp140 wherein the gp41 ectodomain (gp41(ECTO)) occludes the "nonneutralizing" face of gp120, consistent with the antigenic properties of this protein. We also report the application of Blue Native polyacrylamide gel electrophoresis (BN-PAGE), a high-resolution molecular sizing method, to the study of viral envelope proteins. BN-PAGE and other biophysical studies demonstrated that SOS gp140 was monomeric, whereas gp140(UNC) comprised a mixture of noncovalently associated and disulfide-linked dimers, trimers, and tetramers. The oligomeric and conformational properties of SOS gp140 and gp140(UNC) were largely unaffected by purification. An uncleaved gp140 protein containing the SOS cysteine mutations (SOS gp140(UNC)) was also oligomeric. Surprisingly, variable-loop-deleted SOS gp140 proteins were expressed (although not yet purified) as cleaved, noncovalently associated oligomers that were significantly more stable than the full-length protein. Overall, our findings have relevance for rational vaccine design.


Assuntos
Dissulfetos/metabolismo , Produtos do Gene env , Conformação Proteica , Animais , Anticorpos Monoclonais/imunologia , Células CHO , Cricetinae , Dimerização , Produtos do Gene env/química , Produtos do Gene env/genética , Produtos do Gene env/imunologia , Produtos do Gene env/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp41 do Envelope de HIV/metabolismo , Humanos , Microscopia Imunoeletrônica , Modelos Moleculares , Ensaio de Radioimunoprecipitação , Ressonância de Plasmônio de Superfície , Transfecção , Produtos do Gene env do Vírus da Imunodeficiência Humana
16.
IEEE Trans Neural Netw ; 12(2): 181-201, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-18244377

RESUMO

This paper provides an introduction to support vector machines, kernel Fisher discriminant analysis, and kernel principal component analysis, as examples for successful kernel-based learning methods. We first give a short background about Vapnik-Chervonenkis theory and kernel feature spaces and then proceed to kernel based learning in supervised and unsupervised scenarios including practical and algorithmic considerations. We illustrate the usefulness of kernel algorithms by discussing applications such as optical character recognition and DNA analysis.

17.
Bioinformatics ; 16(9): 799-807, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11108702

RESUMO

MOTIVATION: In order to extract protein sequences from nucleotide sequences, it is an important step to recognize points at which regions start that code for proteins. These points are called translation initiation sites (TIS). RESULTS: The task of finding TIS can be modeled as a classification problem. We demonstrate the applicability of support vector machines for this task, and show how to incorporate prior biological knowledge by engineering an appropriate kernel function. With the described techniques the recognition performance can be improved by 26% over leading existing approaches. We provide evidence that existing related methods (e.g. ESTScan) could profit from advanced TIS recognition.


Assuntos
Códon de Iniciação/genética , Biologia Computacional/métodos , Genômica/métodos , Biossíntese de Proteínas/genética , Análise de Sequência de DNA/métodos , Algoritmos , Animais , Bases de Dados Factuais , Humanos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Vertebrados/genética
18.
IEEE Trans Neural Netw ; 10(5): 1000-17, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-18252603

RESUMO

This paper collects some ideas targeted at advancing our understanding of the feature spaces associated with support vector (SV) kernel functions. We first discuss the geometry of feature space. In particular, we review what is known about the shape of the image of input space under the feature space map, and how this influences the capacity of SV methods. Following this, we describe how the metric governing the intrinsic geometry of the mapped surface can be computed in terms of the kernel, using the example of the class of inhomogeneous polynomial kernels, which are often used in SV pattern recognition. We then discuss the connection between feature space and input space by dealing with the question of how one can, given some vector in feature space, find a preimage (exact or approximate) in input space. We describe algorithms to tackle this issue, and show their utility in two applications of kernel methods. First, we use it to reduce the computational complexity of SV decision functions; second, we combine it with the Kernel PCA algorithm, thereby constructing a nonlinear statistical denoising technique which is shown to perform well on real-world data.

19.
J Biochem ; 123(1): 42-6, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9504407

RESUMO

We previously demonstrated that cultured human fibroblasts internalize iron via transferrin-independent iron uptake (Tf-IU), redox, and receptor-mediated endocytosis uptake systems [Oshiro, S., Nakajima, H., Markello, T., Krasnewich, D., Bernardini, I., and Gahl, W.A. (1993) J. Biol. Chem. 268, 21586 21591]. Of these iron transport systems, the Tf-IU system is involved in the accumulation of transition metals in various mammalian cells. It is also known that in experimental animals fed aluminum (Al), Al at micromolar level selectively accumulates in the brain. In the present study, we examined the effects of Al accumulated in the brain cells on iron transport by the Tf-IU system and iron metabolism, using primary cultures from fetal rat cerebral cortex. Pretreatment of cells with 200 microM Al-nitrilotriacetate upregulated the Tf-IU system for iron. Moreover, of various metals tested, Al markedly upregulated the Tf-IU activity. To examine the influence of Al on iron metabolism, the interaction between Al accumulated in the cells and iron-responsive element binding protein (IRE-BP), a cellular iron regulator, was examined by Northern blot analysis, and activity assay: Al decreased the Tf receptor mRNA level and increased the aconitase activity of IRE-BP. The increase of aconitase activity by Al was also observed in vitro. These results suggest that Al accumulated in cortical cells affects iron metabolism.


Assuntos
Alumínio/metabolismo , Córtex Cerebral/metabolismo , Ferro/metabolismo , Transferrina/metabolismo , Aconitato Hidratase/metabolismo , Alumínio/farmacologia , Animais , Cálcio/metabolismo , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Regulação da Expressão Gênica , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismo
20.
Rozhl Chir ; 72(5): 196-8, 1993 Jun.
Artigo em Tcheco | MEDLINE | ID: mdl-8351575

RESUMO

The authors describe the therapeutic results in 135 patients with multiple injuries hospitalized at the Surgical Clinic of the Third Medical Faculty, Charles University in 1981-1990. The authors analyze the procedure in the treatment of these patients which is provided by the most experienced surgeon in collaboration with his assistant. A stage-by-stage procedure and early indication of operation is the most important aspect of treatment.


Assuntos
Traumatismo Múltiplo/cirurgia , Humanos , Traumatismo Múltiplo/etiologia , Traumatismo Múltiplo/patologia
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