From Australopithecus to cyborgs. Are we facing the end of human evolution? / De Australopithecus a cyborgs. ¿Nos enfrentamos al final de la evolución humana? / Do Australopithecus aos ciborgues. Estamos diante do fim da evolução humana?

Abstract Social implementation of post-humanism could affect the biological evolution of living beings and especially that of humans. This paper addresses the issue from the biological and anthropological-philosophical perspectives. From the biological perspective, reference is made first to the evolution of hominids until the emergence of Homo sapiens, and secondly, to the theories of evolution with special reference to their scientific foundation and the theory of extended heredity. In the anthropological-philosophical part, the paradigm is presented according to which human consciousness, in its emancipatory zeal against biological nature, must "appropriate" the roots of its physis to transcend the human and move towards a more "perfect" entity; we also assess the theory that refers this will to the awakening of the cosmic consciousness in our conscious matter. Finally, it assesses whether this post-humanist emancipatory paradigm implies true evolution or, instead, an involution to the primitive state of nature.

Resumen La implementación social del poshumanismo podría afectar la evolución biológica de los seres vivos y, especialmente, la de los humanos. Este artículo aborda el tema desde las perspectivas biológica y antropológico-filosófica. Desde la perspectiva biológica, se hace referencia, en primer lugar, a la evolución de los homínidos hasta la aparición del Homo sapiens, y en segundo lugar a las teorías de la evolución, con especial referencia a su fundamento científico y a la teoría de la herencia extendida. En la parte antropológico-filosófica se presenta el paradigma según el cual la conciencia humana, en su afán emancipador frente a la naturaleza biológica, debe "apropiarse" de las raíces de su physis para trascender lo humano y avanzar hacia una entidad más "perfecta"; evaluamos también la teoría que refiere esta voluntad al despertar de la conciencia cósmica en nuestra materia consciente. Finalmente, evalúa si este paradigma emancipatorio poshumanista implica una verdadera evolución o, en cambio, una involución al primitivo estado de naturaleza.

Resumo A implementação social do pós-humanismo pode afetar a evolução biológica dos seres vivos e especialmente dos humanos. Esse artigo aborda o problema de perspectivas biológicas e antropológico-filosófica. Desde uma perspectiva biológica, é feito referencia primeiro à evolução de hominídeos até a emergência do Homo sapiens e, em seguida, às teorias da evolução, com especial referencia ao seu fundamento científico e à teoria da hereditariedade estendida. Na parte antropológico-filosófica, o paradigma é apresentado de acordo com o qual a consciência humana, em seu zelo emancipatório da natureza biológica, deve "apropriar" as raízes da sua natureza para transcender o humano e se mover em direção a uma entidade mais "perfeita": nós também avaliamos a teoria que refere este desejo ao despertar da consciência cósmica em nossa matéria consciente. Finalmente, ele avalia se este paradigma emancipatório pós-humanista implica evolução verdadeira ou, contrariamente, uma involução para o estado primitivo da natureza.

Analysis of the truth in advertising on the efficacy provided by assisted reproduction clinics / Análisis sobre la autenticidad de la publicidad sobre la eficacia de clínicas de reproducción asistida / Análise da verdade na publicidade sobre a eficácia fornecida pelas clínicas de reprodução assistida

Abstract: This paper analyses the efficacy data from assisted reproduction clinics, obtained from both scientific society reports and from studies published in specialised journals, in order to compare them with information published by Spanish assisted reproduction clinics on their websites. It aims to verify whether this information matches the reality of the findings in the media analysed or, in contrast, differs from the aforementioned scientific evidence. Our study shows marked discrepancies between the evidence of existing statistical data, and figures published by most of the clinics on their websites, which could constitute false advertising.

Resumen: Este estudio analiza los datos de eficacia de clínicas de reproducción asistida, obtenidos tanto de informes de sociedades científicas como de estudios publicados en revistas especializadas, para compararlos con la información publicada por las clínicas de reproducción asistida de España en sus sitios web. El objetivo es verificar si esta información es conforme a los hallados en informes y revistas o, por el contrario, difiere de la evidencia científica mencionada. Nuestro estudio demuestra marcadas discrepancias entre la evidencia de datos estadísticos existentes y las cifras publicadas por la mayoría de los sitios web de las clínicas, lo cual constituye falsa publicidad.

Resumo: Este artigo analisa os dados de eficácia de clínicas de reprodução assistida, obtidas de relatórios da sociedade científica e de estudos publicados em revistas especializadas, a fim de compará-los com informações publicadas por clínicas de reprodução assistida espanholas em seus websites. O artigo visa verificar se esta informação coincide com a realidade dos resultados encontrados nos meios de comunicação analisados ou, por outro lado, difere da evidência científica acima mencionada. Nosso estudo mostra discrepâncias entre a evidência dos dados estatísticos existentes e indicadores publicados pela maioria das clínicas em seus sites, que podem constituir falsa publicidade.

Moral assessment of frozen human embryo adoption in the light of the Magisterium of the Catholic Church / Evaluación moral de la adopción de embriones humanos congelados a la luz del Magisterio de la Iglesia Católica / Avaliação moral de adoção de embriões humanos congelados, em consideração ao Magistério da Igreja Católica

As the number of frozen human embryos continues to rise daily, with numbers not expected to fall, an answer must be found to this dilemma. Four possible solutions have been suggested: a) thaw the embryos and allow them to perish; b) thaw them and donate them for biomedical research; c) thaw them and donate them in adoption; and d) leave them frozen indefinitely. This paper will evaluate the morality of these four possible solutions, particularly frozen human embryo adoption in the light of the Magisterium of the Catholic Church, which in its Instruction Dignitas Personae, appears to have opted to consider this practice as illicit. We also review the various stances of expert moralists in favour of or against frozen human embryo adoption, and we reflect on the extent to which the doctrine contained in Dignitas Personae can bind the moral conscience of the Catholic faithful. Finally, we make a personal evaluation of frozen human embryo adoption, in an attempt to find moral reasons that substantiate the negative opinion manifested by the Catholic Magisterium on this matter. In conclusion, we suggest that the moral assessment of frozen human embryo adoption as set forth in Dignitas Personae might not be considered as settled. Therefore, we are of the opinion that there is no impediment to further research on the moral foundation of this adoptive practice; however, insofar as this occurs, we believe that the best attitude of the Catholic faithful is to follow the moral criteria presented in Dignitas Personae with respect to the adoption of frozen human embryos.

Cada día aumenta el número de embriones humanos congelados y no se prevé que su número disminuya, por lo que parece necesario buscar una solución a este problema. Se han planteado cuatro posibles: a) descongelarlos y dejarlos morir; b) descongelarlos y donarlos para investigaciones biomédicas; c) descongelarlos y donarlos en adopción; y d) dejarlos congelados indefinidamente. En este trabajo se evalúa la moralidad de estas cuatro posibles soluciones, y espacialmente de la adopción de los embriones humanos congelados a la luz del Magisterio de la Iglesia Católica, que en su Instrucción Dignitas Personae, se decanta por la ilicitud de dicha práctica. También se revisan distintas posturas de moralistas expertos favorables o no a la adopción de embriones humanos congelados. Igualmente se reflexiona sobre en qué medida la doctrina contenida en Dignitas Personae puede obligar a la conciencia moral de los fieles católicos. Finalmente se realiza una evaluación personal de la adopción de embriones humanos congelados tratando de buscar razones morales que fundamenten el porqué del juicio negativo manifestado por el Magisterio Católico. Los autores sostienen que la ilicitud ética de la adopción de embriones humanos congelados puede radicar en la ilicitud moral de la subrogación, que hace ilícito todo el proceso procreativo, constituido por: acto conyugal, fecundación del óvulo e implantación del embrión producido en el útero en su madre biológica. Finalmente se plantea que lo expuesto en Dignitas Personae posiblemente no da por zanjada la valoración moral de la adopción de embriones humanos congelados, por lo que somos de la opinión de que no existe impedimento alguno para poder seguir investigando sobre la fundamentación moral de esta práctica adoptiva; pero que, en tanto en cuanto ello se produzca, nos parece que la mejor actitud de los fieles católicos es seguir los criterios morales de Dignitas Personae, expone con respecto a la adopción de embriones humanos congelados.

Cada dia aumenta o número de embriões humanos congelados e não se espera o número diminua, portanto parece necessário encontrar uma solução para este problema. Foram levantadas quatro possíveis: a) descongelá-los e deixá-los morrer; (b) descongelá-los e doá-los para pesquisa biomédica; (c) descongelada-los e doá-los para adoção; e (d) deixá-los congelados indefinidamente. Nesse trabalho se avalia a moralidade dessas quatro possíveis soluções e especialmente a adoção de embriões humanos congelados à luz do Magistério da Igreja Católica, que em sua instrução Dignitas Personae, opta pela ilegalidade da prática. Também se revisam posturas diferentes dos moralistas especialistas favoráveis ou não à adoção de embriões humanos congelados. Igualmente, reflete-se sobre como a doutrina contida na Dignitas Personae pode obrigar a consciência moral dos fiéis católicos.Finalmente se realiza uma avaliação pessoal da adoção de embriões humanos congelados pretendendo buscar razões morais que fundamentem o porquê do juízo negativo manifestado pelo magistério católico. Os autores argumentam que a ilegalidade ética da adoção de embriões humanos congelados pode resultar na ilicitude moral de sub-rogação, tornando ilícito todo o processoprocriador, constiuído por: ato conjugal, fertilização do óvulo e implantação do embrião produzido no útero de sua mãe biológica. Finalmente, apresenta-se que o exposto no Dignitas Personae, possivelmente, não dá por resolvida a valoração moral da adopção de embriões humanos congelados, portanto somos da opinião de que não há nenhum impedimento para seguir pesquisando sobre o fundamentação moral desta prática adotiva; Porém, porquanto ele se produza, parece-nos que a melhor atitude dos fiéis católicos será seguir os critérios morais de Dignitas Personae, expostos no que se refere a adoção de embriões humanos congelados.

Fraude en las publicaciones científicas: una polémica que no cesa / Fraud in scientific publications: a controversy that never ceases

Es un problema ampliamente debatido la existencia de fraudes en la investigación científica, muchas veces debidos a la presión que los investigadores tienen por publicar, pues en ello les va muchas veces la continuidad de sus investigaciones. En este informe se analiza el problema, especialmente a la luz de varias experiencias en las que se han enviado a publicar artículos con contenido intencional fraudulento que han sido admitidos a publicar por revistas especializadas de prestigio

Valoración de la adopción de embriones humanos congelados desde el punto de vista de la filosofía moral, la ética laica y dos religiones monoteístas / Valuating frozen human embryo adoption from a moral philosophical point of view, lay ethics and two monotheist religions / Valoração da adoção de embriões humanos congelados do ponto de vista da filosofia moral, a ética laica e duas religiões monoteístas

La búsqueda de la eficacia en la fecundación in vitro hace que se produzcan más embriones que los que se implantarán, lo que produce un excedente de embriones, que es congelado. Esto hace que ineludiblemente el número de embriones humanos congelados aumente. Entre las soluciones para dichos embriones humanos congelados está la donación/adopción de los mismos. Ineludiblemente esta práctica conlleva objetivos problemas éticos. En este trabajo se evalúa la eticidad de la donación/adopción de embriones humanos congelados desde la perspectiva de la filosofía moral, lo que podríamos llamar una "ética laica" y dos de las religiones monoteístas: la musulmana y la judía.

The search for IVF efficacy leads to a higher embryo production than it is necessary for implantation; this results in an excess of embryos which are kept frozen. This amount of frozen embryos inevitably increases. The donation/adoption are among the possible solutions for these frozen embryos. However, this practice has objective ethical problems. This article considers the ethical aspects of the donation / adoption of frozen human embryos from the point of view of moral philosophy, from what we could call "secular ethics" and from two monotheistic religions: Muslim and Jewish.

A busca da eficácia na fecundação in vitro faz com que se produzam mais embriões dos que se implantarão, o que produz um excedente de embriões, que é congelado. Isto faz com que inquestionavelmente o número de embriões humanos congelados aumente. Entre as soluções para os ditos embriões humanos congelados está na doação/adoção dos mesmos. Ineludivelmente esta prática implica objetivos problemas éticos. Neste trabalho se avalia a eticidade da doação/adoção de embriões humanos congelados a partir da perspectiva da filosofia moral, o que poderíamos chamar uma "ética laica" e duas religiões monoteistas: a mulçumana e a judia.

Use of Embryonic Stem Cells to Treat Severe Eye Diseases.

BACKGROUND: The use of stem cells in regenerative medicine has major therapeutic potential. Recent clinical trials using cells derived from human stem cells are showing encouraging results, although these should be assessed with the necessary caution. DISCUSSION: Some media have reported the results of these trials without due care, perhaps creating expectations that do not match the reality of the facts. This paper describes some of the recent advances in the use of human stem cells, particularly those made in the area of ophthalmology, and more specifically, in Stargardt's disease and age-related macular degeneration (AMD). We also present promising studies with induced pluripotent stem cells (iPS), aimed at obtaining retinal pigmented epithelium and light-sensitive retinal rods in the aforementioned ocular diseases, with encouraging preclinical and clinical results. CONCLUSIONS: From a medical point of view, we must not forget that the transplanted retinal epithelium cells may cause tumours, since they have been obtained from Embryonic Stem cells, and may trigger immune rejection problems since they are heterologous. These considerations attest to the ethical uncertainty of the results of these clinical trials, but above all, it must be stressed that whenever Embryonic Stem cells are used, a human embryo must be destroyed to obtain them, which of course has objective ethical difficulties.

Aborto y salud mental de la mujer / Aborto e saúde mental da mulher / Abortion and the mental health of women

La existencia o no de alteraciones de la salud mental de la mujer como consecuencia del aborto es algo que suscita en el momento actual un vivo debate, pues, junto a convencidos profesionales que defienden su existencia, otros se manifiestan totalmente opuestos a ello. Para abordar este tema hemos evaluado algunas de las más recientes revisiones que nos han parecido de calidad metodológica contrastada, así como también algunos de los últimos artículos publicados. Podemos concluir que no existe un síndrome posaborto como tal, pero sí trastornos psicológicos secundarios al aborto. Finalmente, reflexionamos sobre en qué medida el sentimiento de culpabilidad que la mujer pueda experimentar por haber abortado podría influir en la presentación o no de trastornos psicológicos tras el acto abortivo.

The existence or the lack of alterations of mental health of women as consequence of abortion currently arises a lively debate, since, while there are convinced professionals defending its existence, others are completely opposed to it. In order to examine this issue we have evaluated some of most recent reviews considering they have contrasted methodological value, as well as some of the latest published articles. We can conclude that there is no post abortion syndrome as such, but there are secondary psychological disorders after abortion. Finally, we reflect about in which extent the feeling of guilt that woman may experiment for having aborted may influence the presentation or not of psychological disorders after the abortion act.

A existência ou não de alterações da saúde mental da mulher como consequência do aborto é algo que suscita no momento atual um vivo debate, pois, junto a convencidos profissionais que defendem a sua existência, outros se manifestam totalmente opostos a isso. Para abordar este tema avaliamos algumas das mais recentes revisões que nos pareceram de qualidade metodológica comprovada, assim como também alguns dos últimos artigos publicados. Podemos concluir que não existe uma síndrome pós-aborto como tal, mas sim transtornos psicológicos secundários ao aborto. Finalmente, refletimos sobre em que medida o sentimento de culpabilidade que a mulher pode experimentar por haver abortado poderia influir na apresentação ou não de transtornos psicológicos após o ato abortivo.

El fraude en lappublicación científica: una polémica que no cesa / Fraud in scientffic publishing: a controversy that does not cease / A fraude na puliicação científica: uma polêmica que não cessa

El fraude en la publicación científica supone un lastre para la divulgación de los trabajos de investigación, cuyas causas conviene analizar. A la conducta reprobable de los investigadores que lo cometen puede sumarse el sesgo que las propias publicaciones científicas y buscadores de Internet pueden introducir en los procesos de selección, validación y cálculo de los factores de impacto de los trabajos presentados y publicados. Este artículo ofrece una reflexión al respecto, a raíz de nuevos datos relacionados recientemente publicados.

Fraud in scientific publishing is a drag on the release of research papers, the causes of which should be analyzed. To the reprehensible conduct of researchers who commit fraud one can add the bias the scientific publications and the Internet search engines can introduce to the processes of selection, validation, and calculation of the impact factors of papers already submitted and published. This article offers a reflection on the issue, as a result of related new data having recently been published.

A fraude na publicação científica supõe um obstáculo para a divulgação dos trabalhos de pesquisa, cujas causas convém analisar. À conduta reprovável dos pesquisados que o cometem, pode ser somado o inclinação que as próprias publicações científicas e buscadores de internet podem introduzir nos processos de seleção, validação e cálculo dos fatores de impacto dos trabalhos apresentados e publicados. Este artigo oferece uma reflexão a respeito disso, com base em novos dados relacionados recentemente publicados.

Ethical considerations of universal vaccination against human papilloma virus.

BACKGROUND: From an epidemiological perspective, the practice of universal vaccination of girls and young women in order to prevent human papilloma virus (HPV) infection and potential development of cervical cancer is widely accepted even though it may lead to the neglect of other preventive strategies against cervical cancer. DISCUSSION: It is argued that removing the deterrent effect--the fear of developing cancer--could encourage teenage sex. This paper reflects on the ethical legitimacy of the universal vaccination of girls and young women against HPV infection, especially regarding safety issues, the need to vaccinate people who have opted to abstain from sex, the presumption of early onset of sexual relations, the commercial interests of the companies that manufacture the vaccine, and the recommendation of universal vaccination in males. SUMMARY: Based on the aforementioned information, we believe that the universal vaccination against HPV in young women is acceptable from an ethical point of view, given the medical advantages it presents.

¿Publicar o morir? El fraude en la investigación y las publicaciones científicas / Publish or perihh? fraud in research and scientific publications / Publicar ou moreer? a fraude na pesquisa e nas publicações científiass

La publicación científica, necesaria para el sostenimiento y la divulgación de la labor investigadora, se halla inmersa en la tensión inflacionista que parece afectar a todas las actividades de nuestra sociedad contemporánea. Más exigencia en la producción investigadora, mayor difusión de los trabajos y más necesidad de reconocimiento y promoción personales, son parámetros que parecen condicionar el trabajo de muchos científicos empujándolos hacia la resbaladiza pendiente del fraude. Este trabajo pretende analizar sus causas, naturaleza y dimensiones, de modo que contribuya, si es posible, a establecer nuevas y esperanzadoras vías hacia la investigación honesta de nuestros actuales y futuros científicos.

Scientific publication, so necessary to maintain and circulate research work, is immersed in the inflationary pressure that seems to affect every activity in our contemporary society. More demands on research output, greater dissemination of research work and the need for personal recognition and promotion are the parameters that seem to determine the work of many scientists, pushing them towards the slippery slope of fraud. This paper analyzes its causes, nature and dimensions, so as to contribute, if possible, to creating new and promising paths towards honest research by the scientists of today and tomorrow.

A publicação científica, necessária para o sustento e divulgação do trabalho investigativo, encontra-se imersa na tensão inflacionista que parece afetar todas as atividades de nossa sociedade contemporânea. Mais exigência na produção investigativa, maior difusão dos trabalhos e mais necessidade de reconhecimento e promoção pessoais, são parâmetros que parecem condicionar o trabalho de muitos cientistas e empurra-os à escorregadia ladeira da fraude. Este trabalho pretende analisar suas causas, natureza e dimensões, de modo que contribua, se for possível, para o estabelecimento de novas e esperançosas vias à pesquisa honesta de nossos atuais e futuros cientistas.

Plasminogen activator inhibitor-1 4G/5G polymorphism in breast cancer patients and its association with tissue PAI-1 levels and tumor severity.

BACKGROUND: The plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism may have significance for PAI-1 expression. High levels of PAI-1 in breast cancer patients are associated with a poor prognosis. In this study, we analyzed the influence of the PAI-1 4G/5G polymorphism on tissue PAI-1 levels and its association with tumor severity in women with breast cancer. MATERIAL AND METHODS: We studied 104 women with breast carcinoma (patient group) and 104 healthy age-matched women (control group). In patients and controls, the PAI-1 4G/5G polymorphism was determined by PCR amplification using allele-specific primers. In patients, PAI-1 levels were quantified in breast cancer tissue by using an ELISA. RESULTS: The frequency of the PAI-1 4G allele tended to be higher in patients than in controls (p=0.062). The presence of the 4G allele (4G/5G plus 4G/4G genotypes) was significantly higher among patients with histological grade 3 tumors than among those with grade 1 tumors (p=0.026). Furthermore, patients with the 4G/4G genotype had significantly higher tissue PAI-1 levels than those with the 5G/5G genotype. Moreover, tissue PAI-1 antigen levels were significantly and positively correlated with tumor severity (p=0.003) and tumor size (p=0.009). However, no significant differences in PAI-1 level were observed in relation to menopause, hormone receptor or nodal status. CONCLUSION: Tissue PAI-1 antigen levels and tumor severity seem to be associated with the PAI-1 4G/5G polymorphism. Further studies with a larger number of patients are needed to clarify the influence of this polymorphism in breast cancer.

Red blood cell deformability in iron deficiency anaemia.

In patients with iron deficiency anaemia (IDA) it has been suggested that the shortened erythrocyte lifespan may be in part due to decreased erythrocyte deformability. In order to know whether erythrocyte deformability is decreased in IDA patients, we have determined the erythrocyte Elongation Index (EI) by means of ektacytometric techniques (Rheodyn SSD, Myrenne Gmbh, Germany), in 50 IDA patients and 100 well age and sex matched healthy controls. At the three shear stresses tested, 12, 30 and 60 Pa, IDA patients show statistically lower EI than controls (37.4+/-6.7 vs 48.6+/-2.9; 45.0+/-6.0 vs 54.5+/-2.8; 48.7+/-5.8 vs 57.0+/-2.9 mPa.s, respectively; p<0.001). A statistically significant correlation was found between EI at 12, 30, and 60 Pa and the hematimetric indices (MCV, MCH and MCHC), suggesting that the alteration in surface/volume ratio (shape) which characterizes this kind of microcytic hypocromic anaemia, accounts in part for the decreased EI. Rheodyn SSD, as an ektacytometric technique, is very sensitive to alterations in red blood cell geometry, for what seems to be a useful tool for detecting diminished erythrocyte deformability in IDA patients.

Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry.

Hyperlipidemia is a well established risk factor for cardiovascular disease and atherothrombotic events, in which platelet activation also plays a significant role. However, very few studies have addressed platelet activation in hypercholesterolemia, the potential effect of lipid lowering drugs upon platelet hyperfunction, and the question of whether changes in the latter are correlated to normalization of plasma lipids. This study used whole blood flow cytometry to assess in vivo and in vitro platelet activation in a group of 33 patients with hypercholesterolemia, and also the ex vivo effect of atorvastatin (20 mg/day) upon such activation. A control group of 40 normolipidemic volunteers matched in terms of age, sex and added risk factors to the patient group was used. The results showed that hypercholesterolemic patients had in vivo a significantly greater percentage of GPIIb/IIIa- and phosphatidylserine-positive platelets compared with the control group (4.62+/-3.51% and 2.58+/-1.19% versus 2.73+/-1.08% and 1.54+/-0.68%, respectively). In vitro response of CD62 expression to thrombin was also greater in the patients than in the controls (92.51+/-6.00% versus 89.63+/-10.72%, p<0.05). Atorvastatin therapy normalized platelet hyperfunction in the patients studied and reduced GPIIb/IIIa response to ADP (from 82.65+/-6.43% to 75.84+/-4.89%, p<0.01). A significant correlation can be seen between such normalization and the decrease in plasma levels of total and LDL cholesterol.

The role of the complexed-to-total prostate-specific antigen ratio in predicting the final pathological stage of clinically localized prostate cancer.

OBJECTIVES: To examine the association between the complexed-to-total (C:T) prostate-specific antigen (PSA) ratio and prostate cancer pathological stage to assess whether the C:T PSA ratio may predict the final pathological stage in patients with clinically localized prostate cancer. PATIENTS AND METHODS: In a prospective study, 101 men with clinically localized prostate cancer underwent a staging pelvic lymphadenectomy and radical prostatectomy. Total PSA (tPSA) and PSA complexed to alpha(1)-antichymotrypsin (cPSA) were measured from preoperative plasma and were correlated with the clinical and pathological stage, and with surgical margin status. The pathological stage was determined as organ-confined (n=59) and extracapsular extension (n=42). RESULTS: The distributions of tPSA and cPSA were significantly different in men with locally confined and those with locally extended disease. This finding was not observed for the C:T PSA ratio. The area under the receiver operating characteristic (ROC) curve to predict the final pathological stage was significantly greater for tPSA (0.684) and cPSA (0.677) than for the C:T PSA ratio (p<0.032). TPSA (0.685) and cPSA (0.670) also showed areas under the ROC curve greater than that of the C:T PSA ratio (0.542) (p<0.05) for prediction of positive surgical margins. CONCLUSIONS: Our results show that the C:T PSA ratio does not improve the performance of total PSA for predicting the final pathological stage in patients with clinically localized prostate cancer.

Mutations in the gene encoding the lamin B receptor produce an altered nuclear morphology in granulocytes (Pelger-Huët anomaly).

Pelger-Huët anomaly (PHA; OMIM *169400) is an autosomal dominant disorder characterized by abnormal nuclear shape and chromatin organization in blood granulocytes. Affected individuals show hypolobulated neutrophil nuclei with coarse chromatin. Presumed homozygous individuals have ovoid neutrophil nuclei, as well as varying degrees of developmental delay, epilepsy and skeletal abnormalities. Homozygous offspring in an extinct rabbit lineage showed severe chondrodystrophy, developmental anomalies and increased pre- and postnatal mortality. Here we show, by carrying out a genome-wide linkage scan, that PHA is linked to chromosome 1q41-43. We identified four splice-site, two frameshift and two nonsense mutations in LBR, encoding the lamin B receptor. The lamin B receptor (LBR), a member of the sterol reductase family, is evolutionarily conserved and integral to the inner nuclear membrane; it targets heterochromatin and lamins to the nuclear membrane. Lymphoblastoid cells from heterozygous individuals affected with PHA show reduced expression of the lamin B receptor, and cells homozygous with respect to PHA contain only trace amounts of it. We found that expression of the lamin B receptor affects neutrophil nuclear shape and chromatin distribution in a dose-dependent manner. Our findings have implications for understanding nuclear envelope-heterochromatin interactions, the pathogenesis of Pelger-like conditions in leukemia, infection and toxic drug reactions, and the evolution of neutrophil nuclear shape.

The proportion of prostate-specific antigen (PSA) complexed to alpha(1)-antichymotrypsin improves the discrimination between prostate cancer and benign prostatic hyperplasia in men with a total PSA of 10 to 30 microg/L.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy of the proportion of prostate-specific antigen (PSA) complexed to alpha(1)-antichymotrypsin (PSA-alpha(1)ACT:PSA ratio) in the differential diagnosis of prostate cancer (CaP) and benign prostatic hyperplasia (BPH) in men with total PSA of 10-30 microg/L. METHODS: We used our immunoassays (ELISAs) for total PSA and PSA-alpha(1)ACT complex to study 146 men. In 123, total PSA was between 10 and 20 microg/L; 66 of these had CaP and 57 BPH. In 23 men, total PSA was between 20 and 30 microg/L; 14 of these had CaP and 9 BPH. We calculated the area under the ROC curves (AUC) for total PSA, PSA-alpha(1)ACT complex, and PSA-alpha(1)ACT:PSA ratio, and determined the cutoff points that gave sensitivities approaching 100%. RESULTS: In the total PSA range between 10 and 20 microg/L, the AUC was significantly higher for the PSA-alpha(1)ACT:PSA ratio (0.850) than for total PSA (0.507) and PSA-alpha(1)ACT complex (0.710; P <0.0001). A cutoff ratio of 0.62 would have permitted diagnosis of all 66 patients with CaP (100% sensitivity) and avoided 19% of unnecessary biopsies (11 of 57 patients). In the total PSA range between 20 and 30 microg/L, the AUC for the PSA-alpha(1)ACT:PSA ratio (0.980; 95% confidence interval, 0.82-0.99) was greater than the AUC for total PSA (0.750; 95% confidence interval, 0.51-0.89; P = 0.042). In this range, a cutoff point of 0.64 would have permitted the correct diagnosis of all 14 patients with CaP and 6 of the 9 with BPH. CONCLUSIONS: The diagnostic accuracy of the PSA-alpha(1)ACT:PSA ratio persists at high total PSA concentrations, increasing the specificity of total PSA. Prospective studies with large numbers of patients are needed to assess whether the ratio of PSA-alpha(1)ACT to total PSA is a useful tool to avoid unnecessary prostatic biopsy in patients with a total PSA >10 microg/L.

Quantitative real-time reverse transcription-PCR assay for urokinase plasminogen activator, plasminogen activator inhibitor type 1, and tissue metalloproteinase inhibitor type 1 gene expressions in primary breast cancer.

BACKGROUND: The plasminogen activation system and matrix metalloproteinases (MMPs) play a key role in the degradation of basement membrane and extracellular matrix in tissue remodeling, cancer cell invasion, and metastasis. METHODS: Quantitative real-time reverse-transcription-PCR (RT-PCR) assays were developed to quantify urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue metalloproteinase inhibitor type 1 (TIMP-1) mRNA in 54 breast cancer tissues. Gene fragments were amplified in a LightCycler real-time PCR system using gene-specific primers and SYBR Green I. The results were normalized to beta-actin mRNA. We also quantified antigen and functional concentrations of these components. RESULTS: The intra- and interassay variabilities for mRNA quantification showed mean SDs for the crossing point of 0.12 and 0.15 cycles, respectively. PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and PAI-1 and uPA functional concentrations increased with tumor severity; the increase was statistically significant for PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations and for uPA functional concentrations. Node-positive patients showed significantly higher PAI-1, uPA, and TIMP-1 mRNA and antigen concentrations than those who were node negative. CONCLUSIONS: Quantitative real-time RT-PCR is a highly sensitive, reproducible, and fast method for measuring gene expression of PAI-1, uPA, and TIMP-1 in breast cancer. These components may be involved in breast cancer development, and increased mRNA expression may be associated with a worse prognosis.