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1.
J Strength Cond Res ; 37(7): 1463-1469, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37347945

RESUMO

ABSTRACT: Howarth, DJ, McLean, BD, Cohen, DD, and Coutts, AJ. Sensitivity of countermovement jump variables in professional rugby union players within a playing season. J Strength Cond Res 37(7): 1463-1469, 2023-The aim of this study was to explore the measurement sensitivity of a wide range of countermovement jump (CMJ) variables to a full European professional rugby union season. A secondary purpose was to compare 3 different data treatment methods for the calculation of CMJ variables. Twenty-nine professional rugby union players (mean ± SD; age 24 ± 4 years, height 183.7 ± 8.0 cm, body mass 101.6 ± 10.7 kg) completed a minimum of 12 CMJ testing sessions on Thursdays-a day preceded by a rest day and a minimum of 96 hours after a match-throughout a season. Measurement sensitivity, quantified by signal-to-noise ratio (SNR), was determined for 74 CMJ variables and was calculated by dividing the signal, (week-to-week variation expressed as a coefficient of variation [CV%]) by the noise (interday test/retest reliability expressed as CV%). We also identified variables which had no overlap between the 95% confidence intervals (CIs) for the signal and the noise. The 3 data treatment methods for comparison were (a) mean output across 3 jump trials (Mean3), (b) single output from the trial with the highest jump (BestJH), and (c) the trial with the highest flight time to contraction time ratio (BestFTCT). Most variables had an SNR >1.0 (Mean3 = 60/74; BestFTCT = 59/74; BestJH = 48/74). Fewer variables displayed a nonoverlap of 95% CIs (Mean3 = 23/60; BestFTCT = 22/59; BestJH = 16/48). Most CMJ variables during a professional rugby season demonstrated a signal that exceeded measured noise (SNR > 1.0) and that using the Mean3 or BestFTCT data treatment methods yields a greater number of variables considered sensitive within a season (i.e., SNR > 1.0) than when using BestJH. We also recommend the calculation of the 95% CIs for both signal and noise, with nonoverlap indicative of a greater probability that the responsiveness of the variable at team level (i.e., SNR) also applies at the individual level. As sensitivity analysis is cohort and environment specific, practitioners should conduct a sensitivity analysis using internal signal and noise data to inform their own monitoring protocols.


Assuntos
Desempenho Atlético , Futebol Americano , Humanos , Adulto Jovem , Adulto , Estações do Ano , Reprodutibilidade dos Testes , Rugby , Força Muscular
2.
Artigo em Inglês | MEDLINE | ID: mdl-37359230

RESUMO

As of February 2023, no case has been reported in the U.K., either in the law reports or in the media, of a victim of COVID-19 suing in tort a person or organisation alleged to have caused the victim to contract the disease. This article considers the reasons this situation might have arisen. It provisionally concludes that the main legal reasons might lie in the applicable doctrines of factual causation and goes on to discuss whether uncertainty in those doctrines should be resolved in the courts.

3.
J Strength Cond Res ; 36(11): 3159-3166, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966010

RESUMO

ABSTRACT: Howarth, DJ, Cohen, DD, McLean, BD, and Coutts, AJ. Establishing the noise: interday ecological reliability of countermovement jump variables in professional rugby union players. J Strength Cond Res 36(11): 3159-3166, 2022-The purpose of this study was to examine the interday "ecological" reliability of a wide range of ground reaction force-derived countermovement jump (CMJ) variables. Thirty-six male, professional rugby union players performed 3 CMJs on 4 separate days over an 8-day period during the first week of preseason. We calculated reliability for 86 CMJ variables across 5 interday combinations using 2 criteria: mean output across 3 jump trials (Mean 3 ) and single output from the highest jump (Best JH ). Interday coefficient of variation (CV) of the 86 variables in each CMJ phase, for Mean 3 and Best JH , respectively, ranged between concentric = 2-11% and 2-13%; eccentric = 1-45% and 1-107%; and landing = 4-32% and 6-45%. Mean 3 interday CV was lower in all 86 variables across every interday combination, compared with Best JH . CVs were lower in our cohort than previous studies, particularly for eccentric phase variables. There was no meaningful difference between interday conditions, suggesting any 2-day combination conducted within the first 8 days of preseason, represents a measure of "noise." We did not apply arbitrary reliability "cut-offs" used in previous work (e.g., CV <10%); therefore, our analysis provides reference reliability for a wide range of CMJ variables. However, we recommend that practitioners assess reliability in their athletes, as it is likely to be environment, protocol, and cohort specific.


Assuntos
Desempenho Atlético , Rugby , Humanos , Masculino , Reprodutibilidade dos Testes , Atletas , Estudos de Coortes , Força Muscular
4.
J Neuroophthalmol ; 40(3): 423-427, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32441902

RESUMO

A 70 year-old man presented with insidiously progressing central visual acuity loss in both eyes over several years. Objectively the only abnormality identified on the exam was questionable granularity in the fovea in each eye. Extensive work up which included neuro-imaging, screening blood work for toxic and nutritional causes of optic neuropathy as well as electroretinogram and fluorescein angiography to rule out subtle maculopathy was all unrevealing. When vision continued to deteriorate over the next several years investigations were repeated and again did not yield any positive results. Levels of heavy metals were then obtained after further progression of visual loss, revealing very high levels of arsenic. Subsequent investigations revealed that patient has been spending almost every weekend for the past 28 years alone at a remote country cottage where the sole supply of water was from the local well. He also recalled that 1.5 months after purchasing the cottage he developed hemorrhagic colitis requiring partial colectomy. The specimen from colectomy was located and total reflection x-ray fluorescence testing performed in a specialized lab revealed greatly increased level of arsenic particle in the colonic biopsy from 28 years ago. This case is a reminder that heavy metal toxicity should be considered in a differential diagnosis of patients with bilateral symmetric optic neuropathy.


Assuntos
Intoxicação por Arsênico/complicações , Doenças do Nervo Óptico/induzido quimicamente , Nervo Óptico/patologia , Acuidade Visual , Idoso , Intoxicação por Arsênico/diagnóstico , Doença Crônica , Diagnóstico Diferencial , Progressão da Doença , Eletrorretinografia , Angiofluoresceinografia , Fundo de Olho , Humanos , Masculino , Nervo Óptico/efeitos dos fármacos , Doenças do Nervo Óptico/diagnóstico
5.
Genes Chromosomes Cancer ; 57(9): 437-445, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30014607

RESUMO

Dermatofibrosarcoma protuberans is a locally aggressive superficial mesenchymal neoplasm. It typically occurs in adulthood, and has been reported to have a slight male predilection. Tumors have a characteristic histopathologic appearance, including: storiform architecture, infiltrative "honeycomb" growth within subcutaneous adipose tissue, and immunoreactivity for CD34. Virtually all molecularly characterized cases to date have been found to harbor a COL1A1-PDGFB fusion product. Following identification of an index patient with a novel COL6A3-PDGFD fusion gene, we undertook a molecular investigation, using a combination of RNA sequencing and fluorescence in situ hybridization (FISH), to assess the prevalence of PDGFD rearrangement in dermatofibrosarcoma protuberans (N = 63). Three additional patients were found to have balanced PDGFD rearrangements. Interestingly, all 4 tumors arose on the breast of females. As a result, we subsequently examined 16 additional cases of primary breast dermatofibrosarcoma protuberans, identifying 2 additional tumors with PDGFD rearrangement. The morphology and immunophenotype of all 6 cases was analogous to those with the canonical COL1A1-PDGFB fusion; none of the cases showed fibrosarcomatous transformation. This study illustrates that the COL6A3-PDGFD fusion product is rare in dermatofibrosarcoma protuberans, and associated with an apparent predilection for breast. An awareness of this variant is important for pathologists, as it will not be detected using conventional reverse transcription polymerase chain reaction or FISH-based diagnostic assays for dermatofibrosarcoma protuberans.


Assuntos
Neoplasias da Mama/genética , Colágeno Tipo VI/genética , Dermatofibrossarcoma/genética , Linfocinas/genética , Fator de Crescimento Derivado de Plaquetas/genética , Neoplasias Cutâneas/genética , Adulto , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/isolamento & purificação , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Translocação Genética/genética
7.
Sci Rep ; 12(1): 16919, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209282

RESUMO

Unique identification of optical devices is important for anti-counterfeiting. Physical unclonable functions (PUFs), which use random physical characteristics for authentication, are advantageous over existing optical solutions, such as holograms, due to the inherent asymmetry in their fabrication and reproduction complexity. However, whilst unique, PUFs are potentially vulnerable to replication and simulation. Here we introduce an additional benefit of a small modification to an established model of nanoparticle PUFs by using a second measurement parameter to verify their authenticity. A randomly deposited array of quantum dots is encapsulated in a transparent polymer, forming a tag. Photoluminescence is measured as a function of excitation power to assess uniqueness as well as the intrinsic nonlinear response of the quantum material. This captures a fingerprint, which is non-trivial to clone or simulate. To demonstrate this concept practically, we show that these tags can be read using an unmodified smartphone, with its built-in flash for excitation. This development over constellation-style optical PUFs paves the way for more secure, facile authentication of devices without requiring complex fabrication or characterisation techniques.


Assuntos
Pontos Quânticos , Polímeros , Smartphone
8.
Int J Clin Oncol ; 16(1): 67-70, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20711855

RESUMO

We report an unusual case of a primary osteosarcoma of the lung in an asymptomatic 77-year-old male, who underwent lobectomy with complete resection of the lung lesion. His pattern of relapse was to multiple lymph nodes. The first relapse was 11 weeks after lobectomy in subcarinal lymph nodes, confirmed on needle aspiration to be consistent with sarcoma. Given his excellent performance status, this was treated with radical radiotherapy to 70 Gy in 35 fractions with good control. He relapsed to other lymph node regions. A biopsy of the external iliac lymph node was done and revealed osteoid production, consistent with osteosarcoma. He received palliative radiotherapy to several nodal areas with good clinical response. We review the literature of this rare tumor with an unusual pattern of relapse.


Assuntos
Neoplasias Ósseas/radioterapia , Neoplasias Pulmonares/radioterapia , Recidiva Local de Neoplasia/radioterapia , Osteossarcoma/radioterapia , Idoso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Evolução Fatal , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfonodos/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Tolerância a Radiação
10.
Physiol Meas ; 40(8): 085006, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31422953

RESUMO

OBJECTIVES: Lanthanum (La) and gadolinium (Gd) are known to deposit in bone of exposed populations, namely those who are orally administered lanthanum carbonate (LaC, La2(CO3)3) or are injected with Gd-based contrast agents, respectively. In this work, bone La and Gd concentrations from the environment and diet were measured using x-ray fluorescence in ten post-mortem human tibiae. As a secondary objective, bone barium (Ba) and iodine concentrations were estimated. APPROACH: Two calibration lines were produced for La and Gd and the minimum detection limits (MDLs) of the system were determined using a 180° irradiation-detection geometry. MAIN RESULTS: The MDLs of the system were 0.4 µg La g-1 bone mineral and 0.5 µg Gd g-1 bone mineral. The mean concentrations were -0.02 ± 0.1 µg La g-1 bone mineral and 0.1 ± 0.2 µg Gd g-1 bone mineral in tibiae. The average Ba and iodine concentrations estimated from the experimental La calibration line and Monte-Carlo derived sensitivity factors were determined to be 3.4 ± 0.8 µg Ba g-1 bone mineral and -0.5 ± 0.3 µg iodine g-1 bone mineral. Since it was discovered that four donors previously received an iodine-based contrast agent, the mean concentrations in these donors was 27.8 ± 28.4 µg iodine g-1 bone mineral. SIGNIFICANCE: The XRF system has determined baseline concentrations of these four heavy metals in trace quantities from natural exposure pathways (with the exception of iodine in four donors). This indicates that the system can measure low levels in ex vivo tibiae samples and can potentially be further developed for in vivo studies involving live subjects who are directly exposed to these metals.


Assuntos
Bário/análise , Gadolínio/análise , Iodo/análise , Lantânio/análise , Espectrometria por Raios X , Tíbia/química , Autopsia , Humanos , Limite de Detecção , Método de Monte Carlo , Imagens de Fantasmas
11.
Soc Sci Med ; 222: 198-206, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30660044

RESUMO

Despite the importance of public opinion for policy formation and the political salience of inequality, the public's views about the desirability of equality, not only in health but also in economics and politics, has attracted little attention. We report the results of an on-line survey administered in late 2016 in Great Britain (N = 1667 with a response rate of 35-50%). The survey allowed for testing the sensitivity of public opinion across two other variables: absolute versus relative (everyone should have the same versus inequality should be reduced) and bivariate versus univariate (inequality in one domain is judged in relation to inequality in another versus inequality in a domain is judged independently of other domains). It also allowed examination of how far support for equality in one domain overlaps with support for equality in another. We find that for health, economic and political equality a relative conception of equality attracts more support than an absolute conception, and that for health and political equality a bivariate conception attracts more support than a univariate conception. We also find that conceptions of equality affect how much overlap exists between support for different forms of equality, with a bivariate and relative conception resulting in more overlap than a univariate and absolute conception. We also find evidence for Walzer's 'complex equality' theory in which people tolerate inequality in one domain if it does not control inequality in another.


Assuntos
Disparidades nos Níveis de Saúde , Renda , Política , Opinião Pública , Humanos , Qualidade de Vida , Determinantes Sociais da Saúde , Inquéritos e Questionários , Reino Unido
12.
Virchows Arch ; 452(2): 221-7, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18188596

RESUMO

Erdheim-Chester disease is a rare xanthomatosis that may present with characteristic radiologic and histologic features. There have been conflicting reports regarding the nature of this process, including whether it represents a reactive or neoplastic lesion. We present the clinical histories, pathologic findings, and an analysis of clonality using the HUMARA assay in two patients diagnosed with Erdheim-Chester disease. One case has previously been documented in the literature. Histologically, both cases demonstrated sheets of foamy xanthomatous histiocytes with widespread infiltration of the viscera. These regions were punctuated by variable amounts of inflammation, including lymphocytes, plasma cells, and occasional Touton-type giant cells. The histiocytes were immunoreactive for CD68 and CD163; they did not stain with S100 or CD1a. One case was found to be monoclonal; however, the second case had extensive DNA degradation; thus, clonality could not be assessed. In addition to contributing an additional report of this rare disease to the literature, we demonstrate the histiocytes to express CD163, thereby further supporting a monocyte/macrophage basis. Moreover, in confirming clonality, our observations lend additional evidence to the view that Erdheim-Chester disease represents a neoplastic process.


Assuntos
Células Clonais/patologia , Doença de Erdheim-Chester/patologia , Histiócitos/patologia , Xantomatose/patologia , Adulto , Idoso , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Cromossomos Humanos X , Células Clonais/metabolismo , Doença de Erdheim-Chester/genética , Doença de Erdheim-Chester/metabolismo , Evolução Fatal , Feminino , Histiócitos/metabolismo , Humanos , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Receptores de Superfície Celular/metabolismo , Xantomatose/genética , Xantomatose/metabolismo
13.
J Magn Reson ; 193(1): 1-9, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18342558

RESUMO

In an earlier paper (Part 1), featuring group-theoretical analysis, it was shown that the isotropic EPR spectra of free radical (S=1/2) species XL(n), where the n equivalent nuclei also have spin 1/2, have a more complicated form than anticipated from the usual (first-order) oversimplified analysis. The nucleus of X is taken to be spin-less. The latter predicts n+1 lines with intensity ratios given by the coefficients of the binomial expansion; for systems with n=3, the EPR spectrum in fact consists of 6 lines. Analogous considerations hold for NMR spectroscopy of XL(n) non-radicals. For n > or = 3 systems, the degeneracy of the energy levels cannot be completely removed by the Zeeman electronic and nuclear interactions. Explicit solutions for n=3 (analytic, as well as computational) of the spin-hamiltonian for the energies and spin states have been obtained and are given in the present work. Discussion of the underlying theory, invoking exchange degeneracy, is included herein in some detail, focusing on line positions and relative spectral intensities.

14.
Orbit ; 27(6): 426-31, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19085297

RESUMO

PURPOSE: Solitary fibrous tumor (SFT) occurs rarely in the orbit. We present four such cases, representing one of the largest case series reported to date of this rare orbital tumor. METHOD: The four patients ranged from ages 20 to 50, all of whom presented with lid swelling or bulging in the involved eye. All four patients underwent CT scan to confirm the diagnosis of an orbital mass, which was then excised. RESULTS: The tumors of all four specimens contained spindle-shaped cells with bland nuclei and rare mitotic figures. They all stained positively with CD34 and vimentin. Resection margins were positive in two of the four cases. One of these cases demonstrated residual tumor on follow-up CT scan, which remained unchanged at one-year follow-up. No evidence of residual tumor was found in the other three cases, despite one having malignant pathology. CONCLUSION: SFT is a rare and generally benign tumor of the orbit. Immunohistochemical testing with CD34 is necessary to confirm the diagnosis. Although en bloc tumor resection is the definitive treatment, residual tumor may remain stable for some time. However, this must be followed closely if complete resection is not carried out.


Assuntos
Fibroma/patologia , Neoplasias Orbitárias/patologia , Adulto , Antígenos CD34/análise , Biomarcadores Tumorais/análise , Feminino , Fibroma/química , Fibroma/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Neoplasias Orbitárias/química , Neoplasias Orbitárias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Vimentina/análise
15.
Virchows Arch ; 450(4): 463-70, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17377813

RESUMO

Four cases of malignant PEComas were stained with smooth muscle actin, muscle specific actin, desmin, human melanoma black-45, melan-A, microphthalmia transcription factor, S100 and cyclin D1. One case was studied by electron microscopy (EM). Tumour locations were the thigh, elbow, retroperitoneum and bladder in association with a urachal cyst. There were two men and two women; the average age was 51.3 years, and the size ranged from 5.0-23.0 cm. In three cases, 50-95% of the tumour was composed of pleomorphic sarcomatous areas. All cases had at least focal clear-cell areas. One case showed a continuous single layer of perivascular clear cells remote from the tumour, transitioning to invasive nests and to PEComa. EM demonstrated these cells in apposition to and in direct contact with the abluminal surface of the basal lamina of the capillaries. We suggest the term "pecosis" for these areas. All cases were positive for two or more melanocytic markers and for at least one actin. S100 and desmin were focally positive in one case. Cyclin D1 was positive in 3:4 cases. Four cases of malignant PEComa are described with the existence of a unique lesion (pecosis) in one case. These tumours may manifest largely as sarcomas appearing to be undifferentiated and should be considered in their differential diagnosis.


Assuntos
Biomarcadores Tumorais/análise , Células Epitelioides/patologia , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Actinas/análise , Adulto , Idoso , Antígenos de Neoplasias/análise , Ciclina D1/análise , Desmina/análise , Células Epitelioides/química , Células Epitelioides/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Antígeno MART-1 , Masculino , Antígenos Específicos de Melanoma , Fator de Transcrição Associado à Microftalmia/análise , Microscopia Eletrônica , Pessoa de Meia-Idade , Músculo Liso/química , Proteínas de Neoplasias/análise , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/metabolismo , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/ultraestrutura , Proteínas S100/análise
16.
Can J Ophthalmol ; 41(5): 630-2, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17016539

RESUMO

CASE REPORT: An asymptomatic patient was referred for assessment of an intraocular amelanotic mass in her left eye. Examination showed a mass effect in the inferior location at the 5 o'clock position. This abnormality was defined with ultrasound biomicroscopy and standard ultrasound, but because the appearance was not typical of a melanoma or other choroidal infiltrate, magnetic resonance images and computed tomograms of the orbits were obtained, identifying an extraocular mass arising from the zygomatic rim. Results of a biopsy reported an intraosseous hemangioma. COMMENTS: The diagnosis of intraosseous hemangioma, because of its low incidence and unusual manner of presentation, can be challenging. Computed tomography and biopsy are helpful in making a definitive diagnosis.


Assuntos
Hemangioma/patologia , Neoplasias Orbitárias/patologia , Zigoma/patologia , Idoso , Biópsia , Feminino , Hemangioma/diagnóstico por imagem , Humanos , Neoplasias Orbitárias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Ultrassonografia , Zigoma/diagnóstico por imagem
17.
Cancer Res ; 62(1): 295-300, 2002 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-11782391

RESUMO

Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. Currently, no methods are available for measuring hK11 in biological fluids and tissues. Our aim was to develop immunological reagents and assays for measuring hK11 and examine if the concentration of this kallikrein is altered in disease states. We produced recombinant hK11 protein in a baculovirus system and used it to develop monoclonal and polyclonal antibodies against hK11. We then developed an immunofluorometric procedure for measuring hK11 in biological fluids and tissue extracts with high sensitivity and specificity. We further quantified hK11 in various biological fluids and in serum of patients with various cancers. The hK11 immunofluorometric assay is highly sensitive (detection limit, 0.1 microg/l) and specific (no detectable cross-reactivity for other homologous kallikreins). We established the tissue expression pattern of hK11 at the protein level and found the highest levels in the prostate, followed by stomach, trachea, skin, and colon. We have immunohistochemically localized hK11 in epithelial cells of various organs. We further detected hK11 in amniotic fluid, milk of lactating women, cerebrospinal fluid, follicular fluid, and breast cancer cytosols. However, highest levels were seen in prostatic tissue extracts and seminal plasma. hK11 in seminal plasma and prostatic extracts is present at approximately 300-fold lower levels than prostate-specific antigen and at approximately the same levels as hK2. hK11 expression in breast cancer cell lines is up-regulated by estradiol. Elevated serum levels of hK11 were found in 70% of women with ovarian cancer and in 60% of men with prostate cancer. This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma.


Assuntos
Biomarcadores Tumorais/sangue , Calicreínas/sangue , Neoplasias Ovarianas/enzimologia , Neoplasias da Próstata/enzimologia , Líquido Amniótico/enzimologia , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Baculoviridae/genética , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Calicreínas/biossíntese , Calicreínas/genética , Calicreínas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Leite Humano/enzimologia , Gravidez , Coelhos , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Sêmen/enzimologia
18.
Cancer Res ; 63(24): 9032-41, 2003 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-14695222

RESUMO

Human kallikrein gene 14 (KLK14) is a recently discovered member of the tissue kallikrein family of secreted serine proteases, which includes hK3/prostate-specific antigen, the best cancer biomarker to date. Given that KLK14 is hormonally regulated, differentially expressed in endocrine-related cancers, and a prognostic marker for breast and ovarian cancer at the mRNA level, we hypothesize that its encoded protein, hK14, like hK3/prostate-specific antigen, may constitute a new biomarker for endocrine-related malignancies. The objective of this study was to generate immunological reagents for hK14, to develop an ELISA and immunohistochemical techniques to study its expression in normal and cancerous tissues and biological fluids. Recombinant hK14 was produced in Pichia pastoris, purified by affinity chromatography, and injected into mice and rabbits for polyclonal antibody generation. Using the mouse and rabbit antisera, a sandwich-type immunofluorometric ELISA and immunohistochemical methodologies were developed for hK14. The ELISA was sensitive (detection limit of 0.1 micro g/liter), specific for hK14, linear from 0 to 20 micro g/liter with between-run and within-run coefficients of variation of <10%. hK14 was quantified in human tissue extracts and biological fluids. Highest levels were observed in the breast, skin, prostate, seminal plasma, and amniotic fluid, with almost undetectable levels in normal serum. hK14 concentration was higher in 40% of ovarian cancer tissues compared with normal ovarian tissues. Serum hK14 levels were elevated in a proportion of patients with ovarian (65%) and breast (40%) cancers. Immunohistochemical analyses indicated strong cytoplasmic staining of hK14 by the epithelial cells of normal and malignant skin, ovary, breast, and testis. In conclusion, we report the first ELISA and immunohistochemical assays for hK14 and describe its distribution in tissues and biological fluids. Our preliminary data indicate that hK14 is a potential biomarker for breast and ovarian cancers.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Calicreínas/metabolismo , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Ovarianas/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Linhagem Celular Tumoral , Citosol/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Calicreínas/sangue , Calicreínas/genética , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Neoplasias Ovarianas/sangue , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Sensibilidade e Especificidade
20.
J Magn Reson ; 174(2): 209-18, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15862236

RESUMO

Electron paramagnetic resonance (EPR) spectra of S=1/2 systems XL(n) with n equivalent nuclei having spin I=1/2 have been simulated for microwave frequencies in the L-, X-, and W-bands. It has been shown that for n>2 nuclei, the EPR spectra have a more complicated form than anticipated from the usual oversimplified analysis, which predicts n+1 lines with intensity ratios given by the coefficients of the binomial expansion. For the XL(n) system with n=3, the EPR spectra in fact consist of six lines. The exact solution of the spin-hamiltonian for this case has been obtained, which gives four levels in zero magnetic field. For n>2 systems, the degeneracy of the energy levels cannot be completely removed by the Zeeman electronic and nuclear interactions. For n>4, certain spin states cannot occur, consistent with the (generalized) Pauli exclusion principle. Discussion of the underlying theory, invoking exchange degeneracy and the appropriate permutation group theory, is included in some detail. Analogous considerations hold for NMR spectroscopy of non-radicals.

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