The emergence of Y-chromosome haplogroup J1e among Arabic-speaking populations

Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10 000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations.     

Neonatal liver cirrhosis without iron overload caused by gestational alloimmune liver disease

Gestational alloimmune liver disease has emerged as the major cause of antenatal liver injury and failure. It usually manifests as neonatal liver failure with hepatic and extrahepatic iron overload, a clinical presentation called neonatal hemochromatosis. We report on a newborn in whom fetal hepatomegaly was detected during pregnancy and who presented at birth with liver cirrhosis and mild liver dysfunction. Liver biopsy showed the absence of iron overload but strong immunostaining of hepatocytes for the C5b-9 complex, the terminal complement cascade neoantigen occurring specifically during complement activation by the immunoglobulin G-mediated classic pathway, which established the alloimmune nature of the hepatocyte injury. The infant survived with no specific therapy, and follow-up until 36 months showed progressive normalization of all liver parameters. This case report expands the recognized clinical spectrum of congenital alloimmune liver disease to include neonatal liver disease and cirrhosis, even in the absence of siderosis. Such a diagnosis is of utmost importance regarding the necessity for immunotherapy in further pregnancies to avoid recurrence of alloimmune injury.     

An update on targeted therapy in metastatic renal cell carcinoma

An improved understanding of the biological pathways deregulated in renal cell carcinoma has led to the development of various targeted agents, changing dramatically the therapeutic options for this disease. However, despite numerous opinions and guidelines, the optimal treatment still remains uncertain. In this review, we analyze the most recent published reports regarding the agents sunitinib, bevacizumab, sorafenib, temsirolimus, and everolimus. Moreover, we assess the novel targeted drugs pazopanib and axitinib. In addition, given the likely lack of cross-resistance between these targeting agents, we discuss sequential and combination targeted therapy in metastatic renal cell carcinoma, analyzing the most recent data.     

Psychophysiological reactivity,depression, neuroticism and type a behaviour: An interactive effect?

The greater reactivity in Type A subjects is a controversial issue. It is possible that anxiety, neuroticism and depression interact with Type A behaviour pattern, giving rise to different psychophysiological reactivity. To evaluate this hypothesis we studied 70 Italian healthy male volunteers. All were blue-collar workers. Cardiac health was confirmed by a detailed family and medical history. Individual assessment included the Structured Interview, the Eysenck Personality Questionnaire (EPQ), the State-Trait Anxiety Inventory (STAI) and the Depression Questionnaire (QD). To assess cardiac (rate-pressure product) and electrodermic (skin conductance level) psychophysiological reactivity we used the following tasks: (1) Interactive Concentration Test (ICT); (2) Mental Arithmetic (MAT); (3) Workside Noises (WN). In Type A (A1 + A2) subjects a higher neuroticism score was associated with greater reactivity whereas in non A (X + B) subjects a lower neuroticism score was associated with greater reactivity. Subjects classified as Type A with lower depression scores had greater cardiovascular responses, whereas in non A subjects higher depression scores were associated with greater reactivity.     

Prophylactic oophorectomy: a historical perspective

Removal of a woman's ovaries (known as bilateral oophorectomy, ovariectomy or, historically, ovariotomy) is undertaken in a number of countries. An estimated 19,000 women aged <60 years had a bilateral prophylactic oophorectomy in the UK in 2003, either as a planned response to an increased specific genetic risk of ovarian or breast cancer or, more frequently, as a prophylactic measure to prevent ovarian cancer. Despite its popularity, however, a full evaluation of the risks, costs and benefits of prophylactic oophorectomy in the absence of genetic markers and at the time of hysterectomy has not yet been undertaken. This paper seeks to provide a historical perspective on current practice by outlining approaches to the ovary in Britain from the 19th century onwards. Historically, ovarian removal has raised many questions about the costs and benefits of surgery. The aim of this article is to highlight the issues, and in so doing, to contribute to a more informed assessment of current practice.     

HbF reactivation in sibling BFU-E colonies: synergistic interaction of kit ligand with low-dose dexamethasone

Mechanisms underlying fetal hemoglobin (HbF) reactivation in stress erythropoiesis have not been fully elucidated. We suggested that a key role is played by kit ligand (KL). Because glucocorticoids (GCs) mediate stress erythropoiesis, we explored their capacity to potentiate the stimulatory effect of KL on HbF reactivation, as evaluated in unilineage erythropoietic culture of purified adult progenitors (erythroid burst-forming units [BFU-Es]). The GC derivative dexamethasone (Dex) was tested in minibulk cultures at graded dosages within the therapeutical range (10(-6) to 10(-9) M). Dex did not exert significant effects alone, but synergistically it potentiated the action of KL in a dose-dependent fashion. Specifically, Dex induced delayed erythroid maturation coupled with a 2-log increased number of generated erythroblasts and enhanced HbF synthesis up to 85% F cells and 55% gamma-globin content at terminal maturation (ie, in more than 80%-90% mature erythroblasts). Equivalent results were obtained in unicellular erythroid cultures of sibling BFU-Es treated with KL alone or combined with graded amounts of Dex. These results indicate that the stimulatory effect of KL + Dex is related to the modulation of gamma-globin expression rather than to recruitment of BFU-Es with elevated HbF synthetic potential. At the molecular level, Id2 expression is totally suppressed in control erythroid culture but is sustained in KL + Dex culture. Hypothetically, Id2 may mediate the expansion of early erythroid cells, which correlates with HbF reactivation. These studies indicate that GCs play an important role in HbF reactivation. Because Dex acts at dosages used in immunologic disease therapy, KL + Dex administration may be considered to develop preclinical models for beta-hemoglobinopathy treatment.