TNF-R1 as a first trimester marker for prediction of pre-eclampsia

Objective: To examine whether the maternal serum concentration of the soluble receptor-1 of tumor necrosis factor-α (TNF-R1) at 11–13?+?6 weeks of gestation is a predictor of development of pre-eclampsia (PE).

Methods: This is a nested case–control study in which the concentration of TNF-R1 at 11?+?0 to 13?+?6 weeks was measured in 426 pregnant women in the first trimester. TNF-R1 values were expressed as multiples of the median (MoM) adjusted for maternal factors. The distributions of log TNF-R1 MoM in the control group and hypertensive disorders (early-PE [ePE], late-PE [lPE] and gestational hypertension [GH]) groups were compared. Logistic regression analysis was used to determine whether maternal factors, TNF-R1 or their combination make a significant contribution to the prediction of PE. Screening performance was determined by analysis of receiver–operating characteristics curves.

Results: Median concentration of TNF-R1 (ng/ml) was higher in ePE (2.62?±?0.67), lPE (2.12?±?0.56) and GH (2.19?±?0.45) compared to controls (2.04?±?0.42), p?=?0.001. Logistic regression analysis demonstrated that the addition of TNFR-1 to maternal factors did not make a significant contribution to the prediction of PE.

Conclusions: The maternal serum TNF-R1 concentration at 11–13?+?6 weeks of gestation was increased in pregnancies which developed hypertensive disorders, however, the addition of TNFR-1 did not improve the detection rate of these conditions compared with maternal factors alone.     

Embryology of the testicular descent

Numerous researchers studied the morphology of the testicular descent, including the possible function of the gubernaculum. However, a clear illustration of this process is still missing. The aim of this paper was to illustrate the embryology of the testicular descent in the rat by scanning electron microscopy. In a first phase of the intra-abdominal testicular descent, the testis moves actively from the lower pole of the kidney towards the bladder neck. In a second inguinal phase the testis enters groin and moves in the developing processus vaginalis peritonei caused by the disappearance of the bulb of the gubernaculums testis.     

Cerebral hemiatrophy associated with hippocampal sclerosis following a single prolonged febrile seizure

The etiological relation of prolonged febrile seizures with hippocampal sclerosis and cerebral hemiatrophy is controversial. Causal relationship is mainly adopted from retrospective statistical analysis and data from epilepsy surgery. We report a 17-month-old boy who had a prolonged febrile seizure with a transient postictal flaccid hemiparesis and anisocoria. Family history was unremarkable. Magnetic resonance imaging (MRI) revealed abnormal results in the right hippocampal area where diffusion-weighted sequences showed increased signal intensity consistent with acute neuronal edema. Repeat MRI 5 months later demonstrated sclerosis and atrophy of the right hippocampus in association with an increased T2-weighted signal and atrophy of the right frontal, temporal, and parietal lobe. In addition, 18-fluorodeoxyglucose positron emission tomography and 99mTc-ECD single-photon emission computed tomography revealed glucose hypometabolism and decreased perfusion in the right hemisphere, respectively. A final MRI, 12 months following the seizure, was widely unchanged. Interestingly, during a follow-up of 42 weeks, only minor motor deficits were observed. This case uniquely presents the acute onset of hippocampal sclerosis and, consecutively, cerebral hemiatrophy after a single febrile seizure. This suggests that a single prolonged febrile seizure may cause global morphological changes of the brain, not only affecting hippocampal formation.     

LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus

Cellular attachment factors like the C-type lectins DC-SIGN and DC-SIGNR (collectively referred to as DC-SIGN/R) can augment viral infection and might promote viral dissemination in and between hosts. The lectin LSECtin is encoded in the same chromosomal locus as DC-SIGN/R and is coexpressed with DC-SIGNR on sinusoidal endothelial cells in liver and lymphnodes. Here, we show that LSECtin enhances infection driven by filovirus glycoproteins (GP) and the S protein of SARS coronavirus, but does not interact with human immunodeficiency virus type-1 and hepatitis C virus envelope proteins. Ligand binding to LSECtin was inhibited by EGTA but not by mannan, suggesting that LSECtin unlike DC-SIGN/R does not recognize high-mannose glycans on viral GPs. Finally, we demonstrate that LSECtin is N-linked glycosylated and that glycosylation is required for cell surface expression. In summary, we identified LSECtin as an attachment factor that in conjunction with DC-SIGNR might concentrate viral pathogens in liver and lymph nodes.     

Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome

Defects of mitochondrial polymerase gamma (POLG) underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome. The most severe manifestations have been associated with mutations of the 'spacer' region of POLG, the function of which has remained unstudied in humans. We identified a family, segregating three POLG amino acid variants, A467T, R627Q and Q1236H. The first two affect the spacer region and the third is a polymorphism, allelic with R627Q. Three grades of disease severity appeared to correlate with the genotypes. The patient with the most severe outcome, cerebellar ataxia syndrome, had all three variants, those with R627Q and Q1236H had juvenile-onset ptosis and gait disturbance and those with a single A467T allele had late-onset ptosis. To evaluate the molecular pathogenesis of these spacer defects, we expressed and purified the mutant proteins and studied their catalytic properties in vitro. The A467T substitution resulted in clearly decreased activity, DNA binding and processivity of the polymerase. Our biochemical data, the dominant manifestation of A467T and its previously reported high frequency in the Belgian population (0.6%), emphasize the role of this mutation as a common cause of neurological disease. Further, biochemical evidence that a polymorphic variant may modify the function of a mutant POLG, if occurring in the same polypeptide, is shown here. Finally, and surprisingly, other pathogenic spacer mutants showed DNA-binding affinities and processivities similar to or higher than the controls, suggesting that the disease-causing mechanisms of spacer mutations extend beyond the basic catalytic functions of POLG.     

Behavior of human articular chondrocytes derived from nonarthritic and osteoarthritic cartilage in a collagen matrix

The purpose of this study was to evaluate the morphologic and biochemical behavior and activity of human chondrocytes taken from nonarthritic and osteoarthritic cartilage and seeded on a three-dimensional matrix consisting of collagen types I, II, and III. Human articular chondrocytes were isolated from either nonarthritic or osteoarthritic cartilage of elderly subjects, and from nonarthritic cartilage of an adolescent subject, seeded on collagen matrices, and cultured for 12 h, 7 days, and 14 days. Histological analysis, immunohistochemistry, and biochemical assays for glycosaminoglycans (GAGs) and DNA content were performed for cell-seeded and unseeded matrices. Chondrocytes of nonarthritic cartilage revealed a larger number of spherical cells, consistent with a chondrocytic phenotype. The biochemical assay showed a net increase in GAG content in nonarthritic chondrocytes, whereas almost no GAGs were seen in osteoarthritic cells. The DNA results suggest that more osteoarthritic cells than chondrocytes from nonarthritic cartilage attached to the matrix within the first week. Human articular chondrocytes isolated from osteoarthritic cartilage seem to have less bioactivity after expansion and culture in a sponge consisting of type I, II, and III collagen compared with chondrocytes from nonarthritic cartilage.     

Fine-needle aspiration cytology of pancreatic somatostatinoma: the importance of immunohistochemistry for the cytologic diagnosis of pancreatic endocrine neoplasms

Pancreatic somatostatinoma is a rare pancreatic endocrine neoplasm representing as little as 1% of pancreatic endocrine neoplasms (PENs). The histologic features of this tumor are like those of other PENs, except that it commonly forms acinar structures and often has cells with abundant, granular cytoplasm. We have recently encountered two of these neoplasms sampled by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). We discuss the cytologic and immunohistochemical findings of these two cases and the cytologic similarities these neoplasms share with pancreatic acinar-cell carcinoma (PACC). We review the cytologic features of PEN and PACC and discuss the importance of cell block immunohistochemistry in the diagnosis of pancreatic neoplasia sampled by EUS-guided FNA.     

Analysis of cell type-specific responses mediated by the type IV secretion system of Helicobacter pylori

Helicobacter pylori persistently infects the human stomach and can cause gastritis, gastric ulceration, and gastric cancer. The type IV secretion system (TFSS) of virulent H. pylori strains translocates the CagA protein, inducing the dephosphorylation of host cell proteins and leading to changes in the morphology or shape of AGS gastric epithelial cells. Furthermore, the TFSS is involved in the induction of proinflammatory cytokines. While the H. pylori genes required for TFSS function have been investigated systematically, little is known about possible host cell factors involved. We infected 19 different mammalian cell lines individually with H. pylori and analyzed CagA translocation, dephosphorylation of host cell proteins, chemokine secretion (interleukin-8 and macrophage inflammatory protein 2), and changes in cellular phenotypes. Our results demonstrate that not only bacterial but also host cell factors determine the cellular response to infection. The identification of such unknown host cell factors will add to our understanding of host-pathogen interactions and might help in the development of new therapeutic strategies.     

Preconditioning-specific reduction of c-fos expression in hippocampal granule and pyramidal but not other forebrain neurons of ischemic brain: a quantitative immunohistochemical study

To specify targets for an ischemic preconditioning paradigm (ischemic tolerance), c-fos expressions in ischemic (induced by 10 min bilateral carotid-occlusions subsequent to coagulation of vertebral arteries) and preconditioned rats (treated for 4 min carotid-occlusions 72 h before ischemia) were compared in 12 forebrain areas/nuclei. Fos immunostaining was applied to serial sections of the forebrain and the density (cell number/area measured) of Fos-immunopositive (Fos+) neurons, as well as their percentile changes were determined in five hippocampal and seven extrahippocampal areas/nuclei of ischemic and preconditioned rats. The ratio of counts found in ischemic over control animals showed several fold increase of Fos+ cells in the three layers (granule cell, molecular and polymorphic) of the dentate gyrus, CA3 and CA1 pyramidal neurons, as well as in thalamic and hypothalamic nuclei and limbic cortical areas. In contrast, preconditioning did not alter c-fos expressions significantly in the extrahippocampal brain areas investigated. These results strengthen the hypothesis that the hippocampal and dentate neurons are more susceptible to ischemic tolerance than cells in other brain regions. In fact stress-response and induction of ischemic tolerance in different forebrain areas can be distinguished.