bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD44 and hyaluronate expression in follicular mucinosis
Authors: Kaya Gürkan , Augsburger Eric , Chavaz Pierre , Saurat Jean‐Hilaire 
Published: February 2006

Background:  CD44 is a membrane glycoprotein and the major cell‐surface receptor of hyaluronate (HA). Lack of CD44 expression in mouse epidermis leads to an abnormal HA accumulation in the dermis, indicating an important role of CD44 in local HA metabolism. Decrease of epidermal CD44 expression in patients of lichen sclerosus et atrophicus is potentially responsible for dermal deposition of HA in this disease. Stromal HA accumulation is associated with decreased or lost expression of CD44 in perifollicular solitary cutaneous myxoma, myxoid dermatofibroma, and dermatofibrosarcoma protuberans.Methods:  We examined the expression of CD44 and HA in the skin biopsy specimens of 10 patients with follicular mucinosis by using CD44‐specific antibodies and biotinylated HA‐binding protein (HABP), respectively.Results:  No difference of CD44 expression was observed in the follicular keratinocytes when compared with those of unaffected interfollicular epidermis. The follicular zones of mucin deposition were strongly positive for HA. A weak interkeratinocyte staining for HA was also observed in the interfollicular epidermis. However, HABP staining revealed a stronger reactivity in the follicular keratinocytes surrounding the mucin‐accumulated areas compared to the interfollicular keratinocytes.Conclusion:  Our results suggest an active secretion of HA by follicular cells in follicular mucinosis.
Intravenous immunoglobulin inhibits anti‐glycoprotein IIb‐induced platelet apoptosis in a murine model of immune thrombocytopenia
Authors: Leytin Valery , Mykhaylov Sergiy , Starkey Alison F. , Allen David J. , Lau Herbert , Ni Heyu , Semple John W. , Lazarus Alan H. , Freedman John 
Published: February 2006

SummaryWe have previously shown that injection of anti‐glycoprotein (GP) IIb induces murine immune thrombocytopenia (ITP) and that intravenous immunoglobulin (IVIg) ameliorates ITP. We hypothesise that murine ITP may be associated with platelet apoptosis, which is upregulated by anti‐GPIIb and downregulated by IVIg. The current study demonstrated that anti‐GPIIb injection induced three critical apoptosis manifestations in platelets: (i) mitochondrial inner transmembrane potential (ΔΨm) depolarisation; (ii) caspase‐3 activation; and (iii) phosphatidylserine (PS) exposure. IVIg administration inhibited caspase‐3 activation and PS exposure, but not ΔΨm‐depolarisation, in anti‐GPIIb‐treated platelets, demonstrating that IVIg ameliorates thrombocytopenia concomitantly with inhibiting late, but not early mechanisms of platelet apoptosis.
Spectrum and significance of variants and mutations in the Fanconi anaemia group G gene in children with sporadic acute myeloid leukaemia
Authors: Meyer Stefan , Barber Lisa M. , White Daniel J. , Will Andrew M. , Birch Jillian M. , Kohler Janice A. , Ersfeld Klaus , Blom Eric , Joenje Hans , Eden Tim O. B. , Malcolm Taylor G. 
Published: February 2006

SummaryChildhood acute myeloid leukaemia (AML) is uncommon. Children with Fanconi anaemia (FA), however, have a very high risk of developing AML. FA is a rare inherited disease caused by mutations in at least 12 genes, of which Fanconi anaemia group G gene (FANCG) is one of the commonest. To address to what extent FANCG variants contribute to sporadic childhood AML, we determined the spectrum of FANCG sequence variants in 107 children diagnosed with sporadic AML, using polymerase chain reaction (PCR), fluorescent single‐strand conformational polymorphism (SSCP) and sequencing methodologies. The significance of variants was determined by frequency analysis and assessment of evolutionary conservation. Seven children (6·5%) carried variants in FANCG. Two of these carried two variants, including the known IVS2 + 1G>A mutation with the novel missense mutation S588F, and R513Q with the intronic deletion IVS12‐38 (‐28)_del11, implying that these patients might have been undiagnosed FA patients. R513Q, which affects a semi‐conserved amino acid, was carried in two additional children with AML. Although not significant, the frequency of R513Q was higher in children with AML than unselected cord bloods. While FANCG mutation carrier status does not predispose to sporadic AML, the identification of unrecognised FA patients implies that FA presenting with primary AML in childhood is more common than suspected.
Hereditary pyrimidine 5′‐nucleotidase deficiency: from genetics to clinical manifestations
Authors: Zanella Alberto , Bianchi Paola , Fermo Elisa , Valentini Giovanna 
Published: February 2006

SummaryHereditary pyrimidine 5′‐nucleotidase (P5′N) deficiency is the most frequent abnormality of the red cell nucleotide metabolism causing hereditary non‐spherocytic haemolytic anaemia. The disorder is usually characterised by mild‐to‐moderate haemolytic anaemia associated with the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. The precise mechanisms leading to the destruction of P5′N deficient red cells are still unclear. The pyrimidine 5′‐nucleotidase type‐I (P5′N‐1) gene is localised on 7p15‐p14 and the cDNA has been cloned and sequenced; 20 mutations have been identified so far in 30 unrelated families, most of them at the homozygous level. Recently, the comparison of recombinant mutants of human P5′N‐1 with the wild‐type enzyme has enabled the effects of amino acid replacements on the enzyme molecular properties to be determined and help to correlate genotype to clinical phenotype.
Delayed diagnosis and complications of Fanconi anaemia at advanced age – a paradigm
Authors: Huck Kirsten , Hanenberg Helmut , Gudowius Sonja , Fenk Roland , Kalb Reinhard , Neveling Kornelia , Betz Beate , Niederacher Dieter , Haas Rainer , Göbel Ulrich , Kobbe Guido , Schindler Detlev 
Published: February 2006

SummaryFanconi anaemia (FA) is a rare recessive DNA repair disorder clinically characterised by congenital malformations, progressive bone marrow failure and a high propensity for developing malignancies at an early age, predominantly acute myeloid leukaemia (AML) and squamous cell carcinoma. It is conceivable that a number of patients with hypomorphic mutations are not diagnosed as FA until severe complications in the treatment of a malignancy occur. Here, we report on a patient with FA‐A, diagnosed only at the age of 49 years due to persistent pancytopenia and myelodysplastic syndrome/AML induced by a first cycle of chemotherapy for bilateral metachronic breast cancer. This exceptional case clearly demonstrates that, in instances of long‐lasting mild pancytopenia or development of malignancies, especially at an unusually young age, FA should be ruled out, irrespective of the patient's age and features, especially before inflicting severe genotoxic stress.
Enhanced gene targeting efficiency by siRNA that silences the expression of the Bloom syndrome gene in human cells
Authors: So Sairei , Nomura Yuji , Adachi Noritaka , Kobayashi Yuki , Hori Tamaki , Kurihara Yasuyuki , Koyama Hideki 
Published: February 2006

Gene targeting via homologous recombination is a powerful tool for studying gene function, but the targeting efficiency in human cell lines is too low for generating knockout mutants. Several cell lines null for the gene responsible for Bloom syndrome, BLM, have shown elevated targeting efficiencies. Therefore, we reasoned that gene targeting would be enhanced by transient suppression of BLM expression by RNA interference. To test this, we constructed a gene correction assay system to measure gene targeting frequencies using a disrupted hypoxanthine phosphoribosyltransferase (HPRT) locus in the human HT1080 cell line, and examined the effect of small interfering RNA (siRNA) for BLM on gene targeting. When HPRT‐null cells pretreated with BLM siRNA were co‐transfected with the siRNA and a gene correction vector, the gene targeting frequency was elevated three‐fold, while the random integration frequency was marginally affected. Remarkably, in BLM heterozygous (+/–) cells derived from HPRT‐null cells, the BLM siRNA treatment gave more than five‐fold higher targeting frequencies, even with one‐tenth the amount of BLM siRNA used for BLM+/+ cells. Furthermore, in the human pre‐B cell line Nalm‐6, the siRNA treatment enhanced gene targeting 6.3‐fold and > 5.8‐fold at the HPRT and adenine phosphoribosyltransferase (APRT) loci, respectively. These results indicate that transient suppression of BLM expression by siRNA stimulates gene targeting in human cells, facilitating a further improvement of gene targeting protocols for human cell lines.
Pulmonary involvement by Niemann–Pick disease. A report of six cases
Authors: Nicholson A G , Florio R , Hansell D M , du Bois R M , Wells A U , Hughes P , Ramadan H K , Mackinlay C I , Brambilla E , Ferretti G R , Erichsen A , Malone M , Lantuejoul S 
Published: February 2006

Aims : Although pulmonary involvement is a known cause of morbidity in Niemann–Pick disease, histological features in the lung are not well characterized. The purpose of this study is to document the histological features seen in pulmonary involvement by types B and C Niemann–Pick disease and to correlate them with clinical and imaging data.Methods and results : Surgical lung biopsies from six patients (four with type B and two with type C disease) were reviewed and all showed diffuse endogenous lipid pneumonia, with lesser involvement of the interstitium by fibrosis and foamy macrophage accumulation. In type B disease only, there was also fine cytoplasmic vacuolation within the cytoplasm of ciliated epithelial cells. Neither disease showed foamy changes within pneumocytes. One patient had a bronchial cast removed on whole lung lavage. Electron microscopy showed abnormal lamellar inclusions within lysosomes of affected cells in type B disease. In patients with type C disease, biopsies were undertaken as part of investigations into acute respiratory failure in the context of multiorgan systemic presentation. Three patients with type B disease had clinical disease limited to the lung, all adults (mean age of 40 years) with unexplained diffuse parenchymal lung disease and mainly ground‐glass shadowing on high‐resolution computed tomography.Conclusions : Niemann–Pick disease should be considered for any patient with unexplained diffuse endogenous lipid pneumonia, even when disease is limited to the lungs and presentation is during adulthood.
The foetal Leydig cell – differentiation, function and regulation
Authors: O'Shaughnessy P. J. , Baker P. J. , Johnston H. 
Published: February 2006

SummaryThe foetal Leydig cell population arises shortly after testicular differentiation at around 12.5 dpc in the mouse and 6 weeks in the human. These cells function, primarily, to produce androgens which are essential for masculinization of the foetus. The origin of the foetal Leydig cells remains uncertain but it has been suggested that adrenocortical cells and foetal Leydig cells may share a common origin in an adreno‐genital primordium. Studies in the mouse are beginning to identify factors such as desert hedgehog and platelet‐derived growth factor which are required for foetal Leydig cell development. Regulation of foetal Leydig cell function remains uncertain in most species. Unlike the adult population of Leydig cells, the foetal Leydig cells in the mouse do not require luteinizing hormone (LH) to stimulate androgen production. An intact pituitary does appear to be required, however, and adrenocorticotrophic hormone (ACTH) will stimulate foetal Leydig cell function directly suggesting that both LH and ACTH act to maintain Leydig cell function in vivo. In the human LH/hCG is required for foetal Leydig cell function although the cells may also be sensitive to ACTH.
Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters
Authors: FOSTER PAUL M.D. 
Published: February 2006

SummaryCertain Phthalate esters have been shown to produce reproductive toxicity in male rodents with an age dependent sensitivity in effects with foetal animals being more sensitive than neonates which are in turn more sensitive than pubertal and adult animals. While the testicular effects of phthalates in rats have been known for more than 30 years, recent attention has been focused on the ability of these agents to produce effects on reproductive development in male offspring after in utero exposure. These esters and in particular di‐butyl, di‐(2‐ethylhexyl) and butyl benzyl phthalates have been shown to produce a syndrome of reproductive abnormalities characterized by malformations of the epididymis, vas deferens, seminal vesicles, prostate, external genitalia (hypospadias), cryptorchidism and testicular injury together with permanent changes (feminization) in the retention of nipples/areolae (sexually dimorphic structures in rodents) and demasculinization of the growth of the perineum resulting in a reduced anogenital distance (AGD). Critical to the induction of these effects is a marked reduction in foetal testicular testosterone production at the critical window for the development of the reproductive tract normally under androgen control. A second Leydig cell product, insl3, is also significantly down regulated and is likely responsible for the cryptorchidism commonly seen in these phthalate‐treated animals. The testosterone decrease is mediated by changes in gene expression of a number of enzymes and transport proteins involved in normal testosterone biosynthesis and transport in the foetal Leydig cell. Alterations in the foetal seminiferous cords are also noted after in utero phthalate treatment with the induction of multinucleate gonocytes that contribute to lowered spermatocyte numbers in postnatal animals. The phthalate syndrome of effects on reproductive development has parallels with the reported human testicular dysgenesis syndrome, although no cause and effect relationship exists after exposure of humans to phthalate esters. However humans are exposed to and produce the critical phthalate metabolites that have been detected in blood of the general population, in children and also human amniotic fluid.
Is human fecundity declining?
Authors: Skakkebæk Niels E. , Jørgensen Niels , Main Katharina M. , Meyts Ewa Rajpert‐De , Leffers Henrik , Andersson Anna‐Maria , Juul Anders , Carlsen Elisabeth , Mortensen Gerda Krog , Jensen Tina Kold , Toppari Jorma 
Published: February 2006

SummaryThe decreasing trends in fertility rates in many industrialized countries are now so dramatic that they deserve much more scientific attention. Although social and behavioural factors undoubtedly play a major role for these trends, it seems premature, and not based on solid information, to conclude that these trends can be ascribed to social and behavioural changes alone. There is evidence to suspect that changing lifestyle and increasing environmental exposures, e.g. to endocrine disrupters, are behind the trends in occurrence of male reproductive health problems, including testis cancer, undescended testis and poor semen quality. These biological factors may also contribute to the extremely low fertility rates. However, the necessary research is complex and requires non‐traditional collaboration between demographers, epidemiologists, clinicians, biologists, wild life researchers, geneticists and molecular biologists. This research effort can hardly be carried out without major support from governments and granting agencies making it possible to fund collaborative projects within novel research networks of scientists.
Mouse models for genes involved in impaired spermatogenesis
Authors: O'Bryan M. K. , de Kretser D. 
Published: February 2006

SummarySince the introduction of molecular biology and gene ablation technologies there have been substantial advances in our understanding of how sperm are made and fertilization occurs. There have been at least 150 different models of specifically altered gene function produced that have resulted in male infertility spanning virtually all aspects of the spermatogenic, sperm maturation and fertilization processes. While each has, or potentially will reveal, novel aspects of these processes, there is still much of which we have little knowledge. The current review is by no means a comprehensive list of these mouse models, rather it gives an overview of the potential for such models which up to this point have generally been ‘knockouts’; it presents alternative strategies for the production of new models and emphasizes the importance of thorough phenotypic analysis in order to extract a maximum amount of information from each model.
Neuroendocrine mechanisms controlling female puberty: new approaches, new concepts
Authors: Ojeda Sergio R. , Roth Christian , Mungenast Alison , Heger Sabine , Mastronardi Claudio , Parent Anne‐Simone , Lomniczi Alejandro , Jung Heike 
Published: February 2006

SummarySexual development and mature reproductive function are controlled by a handful of neurones that, located in the basal forebrain, produce the decapeptide luteinizing hormone releasing hormone (LHRH). LHRH is released into the portal system that connects the hypothalamus to the pituitary gland and act on the latter to stimulate the synthesis and release of gonadotrophin hormones. The pubertal activation of LHRH release requires coordinated changes in excitatory and inhibitory inputs to LHRH‐secreting neurones. These inputs are provided by both transsynaptic and glia‐to‐neurone communication pathways. Using cellular and molecular approaches, in combination with transgenic animal models and high‐throughput procedures for gene discovery, we are gaining new insight into the basic mechanisms underlying this dual control of LHRH secretion and, hence, the initiation of mammalian puberty. Our results suggest that the initiation of puberty requires reciprocal neurone‐glia communication involving excitatory amino acids and growth factors, and the coordinated actions of a group of transcriptional regulators that appear to represent a higher level of control governing the pubertal process.
Sperm function tests and fertility
Authors: Aitken R. J. 
Published: February 2006

SummaryTraditionally, the diagnosis of male infertility has depended upon a descriptive evaluation of human semen with emphasis on the number of spermatozoa that are present in the ejaculate, their motility and their morphology. The fundamental tenet underlying this approach is that male fertility can be defined by reference to a threshold concentration of motile, morphologically normal spermatozoa that must be exceeded in order to achieve conception. Many independent studies have demonstrated that this fundamental concept is flawed and, in reality, it is not so much the absolute number of spermatozoa that determines fertility, but their functional competence. In the light of this conclusion, a range of in vitro tests have been developed to monitor various aspects of sperm function including their potential for movement, cervical mucus penetration, capacitation, zona recognition, the acrosome reaction and sperm–oocyte fusion. Such functional assays have been found to predict the fertilizing capacity of human spermatozoa in vitro and in vivo with some accuracy. Recent developments in this field include the introduction of tests to assess the degree to which human spermatozoa have suffered oxidative stress as well as the integrity of their nuclear and mitochondrial DNA. Such assessments not only yield information on the fertilizing capacity of human spermatozoa but also their ability to support normal embryonic development.
Trends in European fertility: should Europe try to increase its fertility rate…or just manage the consequences?1
Authors: Grant Jonathan , Hoorens Stijn , Sivadasan Suja , Loo Mirjam Van Het , Davanzo Julie , Hale Lauren , Butz William 
Published: February 2006

SummaryCurrently across Europe, birth rates are falling and the population is aging. This paper describes these trends and assesses which policies can prevent or mitigate the adverse consequences of these two trends.
Fertility rates and future population trends: will Europe's birth rate recover or continue to decline?
Authors: Lutz Wolfgang 
Published: February 2006

SummaryEurope has long completed its demographic transition from high birth and death rates to low birth and death rates. But the demographic transition paradigm that has been very useful for explaining global demographic trends during the 20th century and that still has strong predictive power when it comes to projecting future trends in countries that still have high fertility, has nothing to say about the future of fertility in Europe. The currently popular notion of a ‘second demographic transition’ is a useful way to describe a bundle of behavioural and normative changes that recently happened in Europe, but it has no predictive power. The social sciences have not yet come up with a useful theory to predict the future fertility level of post‐demographic transition societies. We even do not know whether the trend will be up or down. Given the lack of a predictive theory, this paper will try to do two things: (i) Summarize different substantive arguments that would either suggest the assumption of a recovery of fertility rates in Europe or alternatively, imply further declines. (ii) Convert this discussion of the uncertainty of future fertility trends into probabilistic population projections for Europe, thus highlighting the implications of alternative fertility levels over the coming years. We will also discuss trade‐offs between fertility and immigration, and the phenomenon that Europe now has entered a period of negative momentum of population growth.
Possible impact of phthalates on infant reproductive health
Authors: Lottrup G. , Andersson A.‐M. , Leffers H. , Mortensen G. K. , Toppari J. , Skakkebæk N. E. , Main K. M. 
Published: February 2006

SummaryPhthalates adversely affect the male reproductive system in animals, inducing hypospadias, cryptorchidism, reduced testosterone production and decreased sperm counts. Phthalate effects are much more severe after in utero than adult exposure. Little is known about human health effects. This study discusses two recent studies on perinatal phthalate exposure, which indicated that human testicular development might be susceptible to phthalates. One study analysed phthalate monoesters in breast milk and reproductive hormone levels in infants. Five of six phthalates [monoethyl‐(MEP), monobutyl‐ (MBP), monomethyl‐ (MMP), mono‐2‐ethylhexyl‐ (MEHP) and mono‐isononyl phthalate (MiNP)] showed correlation with hormone levels in healthy boys, which were indicative of lower androgen activity and reduced Leydig cell function. MEP and MBP were positively correlated with serum sex hormone‐binding globulin (SHBG) levels. MMP, MEP, MBP, MEHP and MiNP were positively correlated with the LH/testosterone ratio. Another study found a reduction of the anogenital index (AGI) in infant boys with increasing levels of MBP, MEP, monobenzyl‐ and mono‐isobutyl phthalate in maternal urine samples during late‐pregnancy. Boys with small AGI showed a high prevalence of cryptorchidism and small genital size. Taken together these studies suggest an antivirilizing effect of phthalates in infants. Most of these findings are in line with animal observations. However, the possible effects of MEP appear to be limited to humans. This may be due to differences in exposure routes (inhalation and dermal absorption which circumvents liver detoxification in addition to oral) and metabolism, or this association could be spurious. As phthalates are produced as bulk chemicals worldwide, these new findings raise concern about the safety of phthalate exposure for pregnant women and infants.