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1.
J Strength Cond Res ; 37(8): 1616-1622, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-36728012

RESUMO

ABSTRACT: Amonette, WE, Vazquez, J, and Coleman, AE. Cross-sectional analysis of ground reaction forces during jumps in professional baseball players. J Strength Cond Res 37(8): 1616-1622, 2023-This study described and compared force plate kinetics in major (MLB) and minor (MiLB) baseball players while performing vertical jumps (CMVJ), squat jumps (SSJ), and depth jumps (DJ). Second, comparisons were made between playing positions. Data were collected on 101 professional baseball players. Peak force, eccentric and concentric impulses, peak power, and jump height were determined from each test. Reactive strength index was computed from the DJ. Data were compared using factorial analysis of variances, alpha was set at p ≤ 0.05, and effect sizes were reported using Cohen's d . During CMVJ, MiLB players generated more force ( p = 0.04; d = 0.48), power ( p = 0.02; d = 0.42), and jumped higher ( p = 0.03; d = 0.32) than MLB players. Pitchers generated higher propulsive impulses than catchers ( p = 0.004; d = 0.93). Outfielders generated more power ( p = 0.02; d = 0.98) and jumped higher ( p = 0.049; d = 1.08) than catchers and infielders ( p = 0.025; d = 0.32). Minor league baseball players generated more force ( p = 0.002; d = 0.62), power ( p = 0.001; d = 0.84), and jumped higher ( p = 0.02; d = 0.48) than MLB players in SSJ. No differences were observed by position in SSJ. Minor league baseball players jumped higher than MLB players in the DJ ( p = 0.01; d = 0.57) and outfielders generated more power in the DJ than pitchers ( p = 0.05; d = 0.43) and catchers ( p = 0.007; d = 1.61). Reactive strength index was greater in outfielders compared with catchers ( p = 0.01; d = 1.20). These data indicate that MiLB players were generally more powerful and jumped higher than MLB players in the 3 performance tasks. The difference observed by playing level were likely related to physical preparedness at the beginning of spring training; positional differences were the result of athletic skill sets required for tactical excellence at each position.


Assuntos
Beisebol , Humanos , Estudos Transversais
2.
J Synchrotron Radiat ; 28(Pt 3): 688-706, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33949979

RESUMO

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

3.
Phys Rev Lett ; 123(4): 045701, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31491279

RESUMO

We combined laser shock compression with in situ x-ray diffraction to probe the crystallographic state of gold (Au) on its principal shock Hugoniot. Au has long been recognized as an important calibration standard in diamond anvil cell experiments due to the stability of its face-centered cubic (fcc) structure to extremely high pressures (P >600 GPa at 300 K). This is in contrast to density functional theory and first principles calculations of the high-pressure phases of Au that predict a variety of fcc-like structures with different stacking arrangements at intermediate pressures. In this Letter, we probe high-pressure and high-temperature conditions on the shock Hugoniot and observe fcc Au at 169 GPa and the first evidence of body-centered cubic (bcc) Au at 223 GPa. Upon further compression, the bcc phase is observed in coexistence with liquid scattering as the Hugoniot crosses the Au melt curve before 322 GPa. The results suggest a triple point on the Au phase diagram that lies very close to the principal shock Hugoniot near ∼220 GPa.

4.
Phys Rev Lett ; 122(25): 255704, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31347883

RESUMO

Ultrafast x-ray diffraction at the LCLS x-ray free electron laser has been used to resolve the structural behavior of antimony under shock compression to 59 GPa. Antimony is seen to transform to the incommensurate, host-guest phase Sb-II at ∼11 GPa, which forms on nanosecond timescales with ordered guest-atom chains. The high-pressure bcc phase Sb-III is observed above ∼15 GPa, some 8 GPa lower than in static compression studies, and mixed Sb-III/liquid diffraction are obtained between 38 and 59 GPa. An additional phase which does not exist under static compression, Sb-I^{'}, is also observed between 8 and 12 GPa, beyond the normal stability field of Sb-I, and resembles Sb-I with a resolved Peierls distortion. The incommensurate Sb-II high-pressure phase can be recovered metastably on release to ambient pressure, where it is stable for more than 10 ns.

6.
Phys Rev Lett ; 118(2): 025501, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-28128621

RESUMO

Using x-ray diffraction at the Linac Coherent Light Source x-ray free-electron laser, we have determined simultaneously and self-consistently the phase transitions and equation of state (EOS) of the lightest transition metal, scandium, under shock compression. On compression scandium undergoes a structural phase transition between 32 and 35 GPa to the same bcc structure seen at high temperatures at ambient pressures, and then a further transition at 46 GPa to the incommensurate host-guest polymorph found above 21 GPa in static compression at room temperature. Shock melting of the host-guest phase is observed between 53 and 72 GPa with the disappearance of Bragg scattering and the growth of a broad asymmetric diffraction peak from the high-density liquid.

7.
Physiol Plant ; 160(1): 98-110, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28074485

RESUMO

This study addressed whether the winter annual Arabidopsis thaliana can adjust foliar phloem and xylem anatomy both differentially and in parallel. In plants acclimated to hot vs cool temperature, foliar minor vein xylem-to-phloem ratio was greater, whereas xylem and phloem responded concomitantly to growth light intensity. Across all growth conditions, xylem anatomy correlated with transpiration rate, while phloem anatomy correlated with photosynthetic capacity for two plant lines (wild-type Col-0 and tocopherol-deficient vte1 mutant) irrespective of tocopherol status. A high foliar vein density (VD) was associated with greater numbers and cross-sectional areas of both xylem and phloem cells per vein as well as higher rates of both photosynthesis and transpiration under high vs low light intensities. Under hot vs cool temperature, high foliar VD was associated with a higher xylem-to-phloem ratio and greater relative rates of transpiration to photosynthesis. Tocopherol status affected development of foliar vasculature as dependent on growth environment. The most notable impact of tocopherol deficiency was seen under hot growth temperature, where the vte1 mutant exhibited greater numbers of tracheary elements (TEs) per vein, a greater ratio of TEs to sieve elements, with smaller individual sizes of TEs, and resulting similar total areas of TEs per vein and transpiration rates compared with Col-0 wild-type. These findings illustrate the plasticity of foliar vascular anatomy acclimation to growth environment resulting from independent adjustments of the vasculature's components.


Assuntos
Arabidopsis/efeitos dos fármacos , Arabidopsis/metabolismo , Luz , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Tocoferóis/farmacologia , Fotossíntese/efeitos dos fármacos , Temperatura
8.
BMC Public Health ; 17(1): 211, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28212638

RESUMO

BACKGROUND: The wide-ranging program of reforms brought about by the Health and Social Care Act (2012) in England fundamentally changed the operation of the public health system, moving responsibility for the commissioning and delivery of services from the National Health Service to locally elected councils and a new national public health agency. This paper explores the ways in which the reforms have altered public health commissioning. METHODS: We conducted multi-methods research over 33 months, incorporating national surveys of Directors of Public Health and local council elected members at two time-points, and in-depth case studies in five purposively selected geographical areas. RESULTS: Public health commissioning responsibilities have changed and become more fragmented, being split amongst a range of different organisations, most of which were newly created in 2013. There is much change in the way public health commissioning is done, in who is doing it, and in what is commissioned, since the reforms. There is wider consultation on decisions in the local council setting than in the NHS, and elected members now have a strong influence on public health prioritisation. There is more (and different) scrutiny being applied to public health contracts, and most councils have embarked on wide-ranging changes to the health improvement services they commission. Public health money is being used in different ways as councils are adapting to increasing financial constraint. CONCLUSIONS: Our findings suggest that, while some of the intended opportunities to improve population health and create a more joined-up system with clearer leadership have been achieved, fragmentation, dispersed decision-making and uncertainties regarding funding remain significant challenges. There have been profound changes in commissioning processes, with consequences for what health improvement services are ultimately commissioned. Time (and further research) will tell if any of these changes lead to improved population health outcomes and reduced health inequalities, but many of the opportunities brought about by the reforms are threatened by the continued flux in the system.


Assuntos
Reforma dos Serviços de Saúde/organização & administração , Administração de Serviços de Saúde , Medicina Estatal/organização & administração , Contratos , Inglaterra , Humanos , Liderança
9.
Plant Cell Environ ; 39(7): 1549-58, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26832121

RESUMO

The plasticity of leaf form and function in European lines of Arabidopsis thaliana was evaluated in ecotypes from Sweden and Italy grown under contrasting (cool versus hot) temperature regimes. Although both ecotypes exhibited acclimatory adjustments, the Swedish ecotype exhibited more pronounced responses to the two contrasting temperature regimes in several characterized features. These responses included thicker leaves with higher capacities for photosynthesis, likely facilitated by a greater number of phloem cells per minor vein for the active loading and export of sugars, when grown under cool temperature as opposed to leaves with a higher vein density and a greater number of tracheary elements per minor vein, likely facilitating higher rates of transpirational water loss (and thus evaporative cooling), when grown under hot temperature with high water availability. In addition, only the Swedish ecotype exhibited reduced rosette growth and greater levels of foliar tocopherols under the hot growth temperature. These responses, and the greater responsiveness of the Swedish ecotype compared with the Italian ecotype, are discussed in the context of redox signalling networks and transcription factors, and the greater range of environmental conditions experienced by the Swedish versus the Italian ecotype during the growing season in their native habitats.


Assuntos
Arabidopsis/anatomia & histologia , Folhas de Planta/anatomia & histologia , Temperatura , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Itália , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Transpiração Vegetal , Feixe Vascular de Plantas/crescimento & desenvolvimento , Suécia , Tocoferóis/metabolismo
10.
Br J Dermatol ; 174(1): 165-8, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26595446

RESUMO

BACKGROUND: The current recommended treatment for lentigo maligna (LM) is surgical resection, which can cause significant scarring. The reported recurrence rate after Mohs micrographic surgery is 0-6·25%. There is little published data on long-term outcome after imiquimod therapy. Several reports record progression to LM melanoma during treatment. Clinical assessment of clearance is difficult. Histological confirmation is preferred but risks sampling error and missing areas of invasion. Confocal microscopy can be used to assess entire lesions. OBJECTIVES: To assess the 5-year recurrence rate of LM after imiquimod treatment. METHODS: Forty patients with LM were treated with imiquimod between 2002 and 2007. Their previous treatments included cryotherapy, incomplete surgical excision and radiotherapy. All applied imiquimod three times per week for 6 weeks; 25 (62·5%) experienced inflammation. The other 15 (37·5%) then applied imiquimod five times per week for a further 4 weeks; all experienced inflammation. All patients were subsequently examined and biopsied. Clinical clearance did not always correlate with histological clearance. Eleven patients (27·5%) had residual LM on histology and underwent surgical excision. At the time of this study, three patients had died (deaths were unrelated to LM). Eighteen of the 27 patients (66·7%) who were clear on biopsy after imiquimod attended for the study and were assessed using confocal microscopy (Vivascope 1500 and 3000). RESULTS: The recurrence rate of LM in patients who were clear on histology after imiquimod treatment who attended for this follow-up study was 0% (n = 18). CONCLUSIONS: Imiquimod is an effective long-term treatment for LM. Its use avoids potentially disfiguring surgical resection.


Assuntos
Aminoquinolinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Faciais/tratamento farmacológico , Sarda Melanótica de Hutchinson/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imiquimode , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etiologia
11.
J Public Health (Oxf) ; 38(3): e201-e208, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26487701

RESUMO

BACKGROUND: Following the Health and Social Care Act in England, public health teams were formally transferred from the NHS to local authorities in April 2013. METHODS: Online survey of Directors of Public Health (DsPH) in local authorities in England (n = 152) to investigate their experience within local government 1 year on. Tests of association were used to explore relationships between the perceived integration and influence of public health, and changes in how the public health budget was being spent. RESULTS: The organization of and managerial arrangements for public health within councils varied. Most DsPH felt that good relationships had been established within the council, and the move had made them more able to influence priorities for health improvement, even though most felt their influence was limited. Changes in commissioning using the public health budget were already widespread and included the de-commissioning of services. CONCLUSIONS: There was a widespread feeling amongst DsPH that they had greater influence since the reforms, and that this went across the local authority and beyond. Public health's influence was most apparent when the transfer of staff to local government had gone well, when collaborative working relationships had developed, and when local partnership groups were seen as being effective.


Assuntos
Administração em Saúde Pública , Orçamentos/organização & administração , Humanos , Governo Local , Inovação Organizacional , Administração em Saúde Pública/economia , Administração em Saúde Pública/legislação & jurisprudência , Administração em Saúde Pública/métodos , Administração em Saúde Pública/estatística & dados numéricos , Medicina Estatal/legislação & jurisprudência , Medicina Estatal/organização & administração , Medicina Estatal/estatística & dados numéricos , Inquéritos e Questionários , Reino Unido
12.
J Exp Bot ; 66(2): 541-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25403918

RESUMO

Plant-mediated RNA interference (RNAi) has been successfully used as a tool to study gene function in aphids. The persistence and transgenerational effects of plant-mediated RNAi in the green peach aphid (GPA) Myzus persicae were investigated, with a focus on three genes with different functions in the aphid. Rack1 is a key component of various cellular processes inside aphids, while candidate effector genes MpC002 and MpPIntO2 (Mp2) modulate aphid-plant interactions. The gene sequences and functions did not affect RNAi-mediated down-regulation and persistence levels in the aphids. Maximal reduction of gene expression was ~70% and this was achieved at between 4 d and 8 d of exposure of the aphids to double-stranded RNA (dsRNA)-producing transgenic Arabidopsis thaliana. Moreover, gene expression levels returned to wild-type levels within ~6 d after removal of the aphids from the transgenic plants, indicating that a continuous supply of dsRNA is required to maintain the RNAi effect. Target genes were also down-regulated in nymphs born from mothers exposed to dsRNA-producing transgenic plants, and the RNAi effect lasted twice as long (12-14 d) in these nymphs. Investigations of the impact of RNAi over three generations of aphids revealed that aphids reared on dsMpC002 transgenic plants experienced a 60% decline in aphid reproduction levels compared with a 40% decline of aphids reared on dsRack1 and dsMpPIntO2 plants. In a field setting, a reduction of the aphid reproduction by 40-60% would dramatically decrease aphid population growth, contributing to a substantial reduction in agricultural losses.


Assuntos
Afídeos/genética , Arabidopsis/fisiologia , Padrões de Herança/genética , Interferência de RNA , Animais , Afídeos/crescimento & desenvolvimento , Arabidopsis/genética , Regulação para Baixo/genética , Genes de Insetos , Plantas Geneticamente Modificadas
13.
J Strength Cond Res ; 29(7): 1759-65, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25353082

RESUMO

The purpose of this article was to compare times to first base in Major League Baseball games to determine whether running velocity decreases to the foul line and first base among players with differing years of playing experience. From 1998 to 2012, 1,185 sprint times to first base were analyzed: 469 outfielders, 601 infielders, and 115 catchers. The players were divided into differing experience categories depending on their years of service in Major League Baseball: 1-5, 6-10, 11-15, and 16-20+ years. Velocity at the foul line and first base was compared and interval accelerations were reported. Comparisons were completed by playing position, and within left- and right-handed batters. Left-handed outfielders exhibited reduced velocities at 6-10 (p = 0.04), 11-15 (p = 0.004), and 16-20 years (p < 0.001) compared with 1-5 years; there were no statistical differences in velocity at the foul line. Right-handed outfielders exhibited significantly reduced velocities at first base in 6-10 (p = 0.002) and 11-15 years (p = 0.001); they also had a reduced velocities at the foul line in 6-10 (p = 0.004) and 11-15 years (p = 0.009). Right-handed infielders had reduced velocities at first base in 11-15 years (p < 0.001). No other differences were observed within infielders at first base or the foul line. There were no differences within the compared variables for catchers. Decreases in running velocity to first base with experience are seen in outfielders but are less prominent in infielders and catchers. Although physical capabilities for sprinting may decline with age, it is possible that through repetition more experienced players perfect the skill-related component of running to first base, thus preserving speed.


Assuntos
Aceleração , Beisebol/fisiologia , Corrida/fisiologia , Adolescente , Adulto , Estudos Transversais , Mãos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
14.
Psychiatr Q ; 86(3): 419-33, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25601029

RESUMO

There is a pressing need to develop community interventions that will address stigma against mental illness in rural India. This cross-sectional study will compare social representations of depression in villages where educational programs have targeted mental illness and stigma versus control villages. Participants from the villages exposed to the educational interventions (n = 146) will be compared with a sample from six control villages (n = 187) in the same geographic region, using a structured questionnaire. The impact of the intervention as a predictor for questionnaire score will be assessed along with socio-demographic variables. The intervention villages showed higher levels of literacy regarding depression and lower levels of stigma, after adjusting for all other socio-demographic variables. While some demographic factors associated with the knowledge and attitudes towards depression are not modifiable, our research provides evidence in favor of the positive influence a community grassroots intervention can have on mental health literacy in rural settings.


Assuntos
Depressão/psicologia , Conhecimentos, Atitudes e Prática em Saúde , População Rural , Estigma Social , Adolescente , Adulto , Idoso , Feminino , Educação em Saúde , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Características de Residência , Adulto Jovem
15.
J Vet Cardiol ; 51: 124-137, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128418

RESUMO

INTRODUCTION/OBJECTIVES: Manual compression has been standard of care for maintaining hemostasis after percutaneous endovascular intervention, but can be time-consuming and associated with vascular complications. Alternative closure methods include the figure-of-eight suture (Z-stitch) and vascular closure device (VCD) techniques. We hypothesized that compared to manual compression, Z-stitch and VCD would significantly reduce time-to-hemostasis after transvenous access, and the proportion of dogs with vascular patency would not differ significantly among treatments. ANIMALS: Forty-six client-owned dogs undergoing percutaneous transvenous interventional procedures. MATERIALS AND METHODS: Dogs with vessel diameter <5 mm were randomized to undergo manual compression or Z-stitch, while those with vessel diameter ≥5 mm were randomized to undergo manual compression, Z-stitch, or VCD. Time-to-hemostasis, bleeding scores, presence of vascular patency one day and two to three months post-procedure, and complications were recorded. Data are presented as median (95% confidence interval). RESULTS: In all 46 dogs, the right external jugular vein was used. Time-to-hemostasis was significantly shorter in the Z-stitch (2.1 [1.8-2.9] minutes) compared to VCD (8.6 [6.1-11.8] minutes; P<0.001) and manual compression (10.0 [10.0-20.0] minutes; P<0.001) groups. Time-to-hemostasis was significantly shorter in the VCD vs. manual compression (P=0.027) group. Bleeding scores were significantly greater at 5 and 10 min (P<0.001 and 0.013, respectively) in manual compression, compared to Z-stitch group. There was no difference in the proportion of dogs with vascular patency between groups (P=0.59). CONCLUSIONS: Z-stitch and VCD are effective venous hemostasis methods after percutaneous transvenous intervention, with Z-stitch providing the most rapid time-to-hemostasis. Both Z-stitch and VCD techniques have low complication rates and effectively maintain vascular patency.


Assuntos
Doenças do Cão , Técnicas Hemostáticas , Hemorragia Pós-Operatória , Dispositivos de Oclusão Vascular , Procedimentos Cirúrgicos Vasculares , Animais , Cães , Doenças do Cão/cirurgia , Artéria Femoral/cirurgia , Técnicas Hemostáticas/efeitos adversos , Técnicas Hemostáticas/veterinária , Resultado do Tratamento , Dispositivos de Oclusão Vascular/veterinária , Dispositivos de Oclusão Vascular/efeitos adversos , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/instrumentação , Procedimentos Cirúrgicos Vasculares/métodos , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/veterinária
16.
J Vet Cardiol ; 51: 86-96, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38118234

RESUMO

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.


Assuntos
Sotalol , Gatos , Animais , Estudos Cross-Over , Infusões Intravenosas/veterinária , Cromatografia Líquida de Alta Pressão/veterinária , Disponibilidade Biológica , Administração Oral , Meia-Vida
17.
Nat Genet ; 14(3): 312-5, 1996 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8896561

RESUMO

Murine models of human carcinogenesis are exceedingly valuable tools to understand genetic mechanisms of neoplastic growth. The identification of recurrent chromosomal rearrangements by cytogenetic techniques serves as an initial screening test for tumour specific aberrations. In murine models of human carcinogenesis, however, karyotype analysis is technically demanding because mouse chromosomes are acrocentric and of similar size. Fluorescence in situ hybridization (FISH) with mouse chromosome specific painting probes can complement conventional banding analysis. Although sensitive and specific, FISH analyses are restricted to the visualization of only a few mouse chromosomes at a time. Here we apply a novel imaging technique that we developed recently for the visualization of human chromosomes to the simultaneous discernment of all mouse chromosomes. The approach is based on spectral imaging to measure chromosome-specific spectra after FISH with differentially labelled mouse chromosome painting probes. Utilizing a combination of Fourier spectroscopy, CCD-imaging and conventional optical microscopy, spectral imaging allows simultaneous measurement of the fluorescence emission spectrum at all sample points. A spectrum-based classification algorithm has been adapted to karyotype mouse chromosomes. We have applied spectral karyotyping (SKY) to chemically induced plasmocytomas, mammary gland tumours from transgenic mice overexpressing the c-myc oncogene and thymomas from mice deficient for the ataxia telangiectasia (Atm) gene. Results from these analyses demonstrate the potential of SKY to identify complex chromosomal aberrations in mouse models of human carcinogenesis.


Assuntos
Aberrações Cromossômicas , Cromossomos , Cariotipagem/métodos , Proteínas Serina-Treonina Quinases , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Modelos Animais de Doenças , Genes myc , Humanos , Hibridização in Situ Fluorescente/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos , Camundongos Transgênicos , Neoplasias/genética , Plasmocitoma/genética , Proteínas/genética , Proteínas Supressoras de Tumor
18.
Clin Exp Immunol ; 170(2): 212-21, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23039892

RESUMO

Dendritic cells (DC) in HIV-1-infected individuals are decreased and their dysfunction has been implicated in HIV-1 immunopathogenesis. The mechanism of their dysfunction remains unclear, thus we analysed the expression of membrane molecules associated with immune regulation and DC activation in myeloid (mDC) and plasmacytoid DC (pDC) in therapy-naive and highly active anti-retroviral therapy (HAART)-treated HIV-1(+) patients. DC from healthy controls, untreated HIV-1(+) and HAART-treated patients were assessed by flow cytometry for expression of: anergy and apoptosis inducing molecules [programmed death (PD)-1 and its ligands PD-L1 and PD-L2], inhibitory and regulatory T cell-inducing molecules [immunoglobulin-like transcript (ILT)-3 and ILT-4], interferon (IFN)-α inhibitory receptor (ILT-7) and co-stimulatory molecules (CD80, CD83, and CD86). pDC from untreated HIV-1(+) patients expressed significantly lower levels of ILT-7 compared to healthy controls, while HAART-treated patients showed normal expression. pDC were also found to express moderately higher levels of PD-L1 and ILT-3 and lower levels of PD-L2 receptors in untreated patients compared to controls and HAART-treated patients. No significant changes were observed in mDC. There were no associations between the percentages and levels of expression of these molecules by pDC and viral load or CD4 T cell count. In conclusion, pDC but not mDC from HIV-1(+) patients with active viraemia display higher levels of apoptosis and T regulatory-inducing molecules and may be predisposed to chronically produce IFN-α through down-regulation of ILT-7. HAART restored normal expression levels of these receptors.


Assuntos
Células Dendríticas/imunologia , Infecções por HIV/imunologia , Células Mieloides/imunologia , Adulto , Antígenos CD/imunologia , Antígenos CD/metabolismo , Terapia Antirretroviral de Alta Atividade/métodos , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Estudos de Coortes , Células Dendríticas/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Infecções por HIV/patologia , HIV-1/imunologia , Humanos , Imunofenotipagem , Masculino , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Células Mieloides/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Superfície Celular/imunologia , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/imunologia , Receptores Imunológicos/metabolismo , Viremia/imunologia , Viremia/metabolismo , Adulto Jovem
19.
Ann Surg Oncol ; 19(12): 3896-3905, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22549288

RESUMO

BACKGROUND: Isolated limb infusion with melphalan (ILI-M) corrected for ideal body weight (IBW) is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximate 29 % complete response (CR) rate. Sorafenib, a multi-kinase inhibitor, has been shown to augment tumor response to chemotherapy in preclinical studies. METHODS: A multi-institutional, dose-escalation, phase I study was performed to evaluate the safety and antitumor activity of sorafenib in combination with ILI-M. Patients with AJCC stage IIIB/IIIC/IV melanoma were treated with sorafenib starting at 400 mg daily for 7 days before and 7 days after ILI-M corrected for IBW. Toxicity, drug pharmacokinetics, and tumor protein expression changes were measured and correlated with clinical response at 3 months. RESULTS: A total of 20 patients were enrolled at two institutions. The maximum tolerated dose (MTD) of sorafenib in combination with ILI-M was 400 mg. Four dose-limiting toxicities occurred, including soft tissue ulcerations and compartment syndrome. There were three CRs (15 %) and four partial responses (20 %). Of patients with the Braf mutation, 83 % (n = 6) progressed compared with only 33 % without (n = 12). Short-term sorafenib treatment did alter protein expression as measured with reverse phase protein array (RPPA) analysis, but did not inhibit protein expression in the MAP kinase pathway. Sorafenib did not alter melphalan pharmacokinetics. CONCLUSION: This trial defined the MTD of systemically administered sorafenib in combination with ILI-M. Although some responses were seen, the addition of sorafenib to ILI-M did not appear to augment the effects of melphalan but did increase regional toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Extremidades/patologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Feminino , Seguimentos , Humanos , Masculino , Dose Máxima Tolerável , Melanoma/patologia , Melfalan/administração & dosagem , Estadiamento de Neoplasias , Niacinamida/administração & dosagem , Niacinamida/análogos & derivados , Compostos de Fenilureia/administração & dosagem , Prognóstico , Análise Serial de Proteínas , Neoplasias Cutâneas/patologia , Sorafenibe , Distribuição Tecidual
20.
Clin Exp Dermatol ; 37(3): 219-26, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22277060

RESUMO

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.


Assuntos
Dermatopatias/radioterapia , Terapia Ultravioleta/métodos , Acessibilidade aos Serviços de Saúde , Humanos , Terapia Ultravioleta/efeitos adversos , Reino Unido
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