The KBG syndrome: confirmation of autosomal dominant inheritance and further delineation of the phenotype

We report on a Turkish family in which the father and his two sons were diagnosed as having the KBG syndrome. Large upper central incisors were the diagnostic finding in all three patients along with mental retardation, cryptorchidism, skeletal abnormalities, and short stature. Our report clearly confirms that the inheritance is autosomal dominant in KBG syndrome, although a high male to female ratio has been observed in published cases.     

Interactions between human and porcine interferons.

To investigate the possible interactions between human and porcine interferons (IFNs) in vitro, human transformed (FL) and nontransformed (HEF) cells were treated with either HuIFN alpha and/or gamma and porcine alpha and/or gamma. In both cases the antiproliferative activity was measured to determine the effects of different combinations between human and porcine IFNs on cell proliferation. Combinations of human and porcine IFNs acted mostly antagonistically with exception of IFN combination Hu-alpha/Po-gamma which showed a synergic cooperativity in therms of antiproliferative activity on human transformed cells.     

Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis

Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.     

Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis

The effectiveness of galactomannan detection with the Platelia test was evaluated in a prospective study of 3,327 sera from 807 patients. The specificity was 99.6% (748 of 751 cases). For the groups of patients with proven and probable invasive aspergillosis, the sensitivity was 50.0% (17 of 34 cases). The disappointing sensitivity associated with the presence of rare false-positive cases underlines the limits of this test.     

2Mouse PAI-1 promotes placentation by increasing foetal and maternal angiogenesis

Introduction: Murine placentation is associated with trophoblast cells invasion of the maternal endometrium and extensive maternal and foetal angiogenesis. Both processes involve proteases‐dependent extracellular matrix remodelling. Among the protease inhibitors, plasminogen activator inhibitor‐1 (PAI‐1) is transiently produced by spongiotrophoblasts and trophoblast giant cells at days 10.5‐11.5 day post‐coitum (dpc). Although accumulating evidence demonstrates the key role of PA‐1 in pathological angiogenesis, its function during placental vascularisation remains to be elucidated. PAI‐1 knockout mice are fertile and the litter sizes are normal. We have therefore analysed the consequence of PAI‐1 deficiency on murine placentation. Material and Methods: We have studied the possible role of PAI‐1 by quantitating the placental vessel density, the relative thickness of the labyrinth, decidua and spongiotrophoblast at day 10.5, 12.5 and 14.5 dpc in mice deficient for PAI‐1 or in control mice. An original method of computer‐assisted image analysis allowed us to quantify alterations of several placental compartments identified with specific monoclonal antibodies (keratin, desmin, fibrinogen and MECA‐32). To investigate the differentially expressed genes, we performed laser capture microdissection (LCM), followed by genome‐wide expression profiling using high‐density oligonucleotides microarray analysis (GeneChip Mouse Genome 430 2.0 Array, Affymetrix). Data were analysed using Ingenuity Pathways Analysis (Ingenuity Systems^®, http://www.ingenuity.com ). Results: At 10.5 and 12.5 dpc, an abnormal placental morphology was observed in both labyrinth and spongiotrophoblast layers in PAI‐1‐/‐ mice. Lack of PAI‐1 resulted in a transient decreased maternal and fetal vascularisation of the placenta that caused (1) an enhancement in the decidua/labyrinth and labyrinth/spongiotrophoblast thickness ratios, (2) a significant increase of trophoblast density. Normalization of placental morphology occurred by day 14.5 dpc in PAI‐1 deficient mice. Statistical analysis of microarrays revealed 706 genes differentially expressed between PAI‐1 deficient and normal mice in the labyrinth zone at 10.5 dpc. At 14.5 dpc, only 205 genes are differentially expressed. Using Ingenuity Pathways Analysis, most of those genes were found to be associated to lipid metabolism, cellular growth and proliferation. Conclusion: Despite a transient PAI‐1 requirement for optimal placental angiogenesis, this gene does not appear to be essential for trophoblast invasion and placentation.     

Neuromuscular changes after long-lasting mechanically and electrically elicited fatigue

Central fatigue was investigated under an isolated active condition whereby the possible effects of supraspinal fatigue were minimized. Therefore, ten subjects were fatigued by simultaneously and repeatedly mechanically stretching and electrically stimulating their calf muscles for 1 h. This was performed using an ankle ergometer. The active fatigue task included a total of 2400 muscle stretches with an intensity of 10% of the maximal voluntary contraction (MVC). This protocol clearly impaired neuromuscular function, as revealed by a significant reduction in MVC (P<0.01) and the neural input to the muscle (average EMG) (P<0.01–0.001). The interpolated nerve stimulation compensated for this force loss by 4.28% (P<0.05). Stretch-reflex recordings revealed a notable post-fatigue reduction in the peak-to-peak amplitude (59.1%, P<0.01) and stretch-resisting force of the muscle (14.1%, P<0.01). The maximal H-reflex declined by 50.5% (P<0.001) and did not recover while the leg was kept ischemic. It is suggested that the existing protocol with minor metabolic loading can induce central fatigue, which seems to be of reflex origin from the fatigued muscle. Although the role of presynaptic inhibition of Ia terminals is possibly reinforced, disfacilitation via reduced spindle sensitivity cannot be excluded. Electronic Publication     

A novel fungal prenyl diphosphate synthase in the dimorphic zygomycete Mucor circinelloides

Two Mucor circinelloides structural genes involved in isoprenoid biosynthesis were isolated and characterised. The isoA gene encodes a typical eukaryotic farnesyl diphosphate synthase (EC 2.5.1.10), whereas the isoB gene deduced amino acid sequence shows similarity to fungal medium-chain prenyl diphosphate synthases. By functional complementation in Escherichia coli, the isoB gene product was shown to be a solanesyl diphosphate synthase (EC 2.5.1.11), which is the first fungal enzyme reported having this specificity. In addition, a M. circinelloides one-marker-per-chromosome map was completed by contour-clamped homogeneous electric field localisation of isoA, isoB and three other isoprenoid biosynthesis genes to individual chromosomes.Abbreviations FPP farnesyl diphosphate (or pyrophosphate) - GGPP geranylgeranyl diphosphate - PrenylPP prenyl diphosphate - DPP decaprenyl diphosphate - HPP hexaprenyl diphosphate - SPP solanesyl diphosphate     

Impaired responses to toll-like receptor 4 and toll-like receptor 3 ligands in human cord blood

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.