The human premotor oculomotor brainstem system – can it help to understand oculomotor symptoms in Huntington's disease?

Recent progress in oculomotor research has enabled new insights into the functional neuroanatomy of the human premotor oculomotor brainstem network. In the present review, we provide an overview of its functional neuroanatomy and summarize the broad range of oculomotor dysfunctions that may occur in Huntington's disease (HD) patients. Although some of these oculomotor symptoms point to an involvement of the premotor oculomotor brainstem network in HD, no systematic analysis of this functional system has yet been performed in brains of HD patients. Therefore, its exact contribution to oculomotor symptoms in HD remains unclear. A possible strategy to clarify this issue is the use of unconventional 100-µm-thick serial tissue sections stained for Nissl substance and lipofuscin pigment (Nissl-pigment stain according to Braak). This technique makes it possible to identify the known nuclei of the premotor oculomotor brainstem network and to study their possible involvement in the neurodegenerative process. Studies applying this morphological approach and using the current knowledge regarding the functional neuroanatomy of this human premotor oculomotor brainstem network will help to elucidate the anatomical basis of the large spectrum of oculomotor dysfunctions that are observed in HD patients. This knowledge may aid clinicians in the diagnosis and monitoring of the disease.     

WASP gene mutations in Wiskott-Aldrich syndrome and X-linked thrombocytopenia

The WASP gene has been recently cloned from Xp11.23 and shownto be mutated in three patients with the Wiskott-Aldrich syndrome(WAS). We have developed a screening protocol for identifyingWASP gene alterations in genomic DNA and have identified a spectrumof novel mutations In 12 additional unrelated families. Thesemissense, nonsense and frameshift mutations involve eight ofthe 12 exons of the gene. Two mutations creating premature terminationcodons were associated with lack of detectable mRNA on Northernblots. Four amino acid substitutions, Leu27Phe, Thr48lle, Val75Metand Arg477Lys, were found In patients with congenital thrombocytopeniaand no clinically evident immune defect indicating that theWASP gene is the site for mutations in X-linked thrombocytopeniaas well as in WAS. A T-cell line from a WAS patient containedtwo independent DNA alterations, a constitutional frameshiftmutation, also present in peripheral blood leukocytes from thepatient, and a compensatory splice site mutation unique to thecell line. The distribution of eight missense mutations providesvaluable information on amino acids which are essential fornormal protein function, and suggests that sites in the firsttwo exons are hot-spots for mutation.     

Xeromammographic automatic exposure termination

A method of automatic exposure termination (AET) for xeromammography has been devised, significantly reducing the rate of repeat exposures due to poor choice of manual exposure factors. AET images are of good quality and are reliably produced. The concept of AET is based on the existence of an optimal transmitted exposure to the selenium plate, which is easily determined experimentally. In routine clinical xeromammography, a repeat rate of 20% was eliminated by the use of AET.     

Maternal IL-11Rα function is required for normal decidua and fetoplacental development in mice

In eutherian mammals, implantation and establishment of the chorioallantoic placenta are essential for embryo development and survival. As a maternal response to implantation, uterine stromal cells proliferate, differentiate, and generate the decidua, which encapsulates the conceptus and forms the maternal part of the placenta. Little is known about decidual functions and the molecular interactions that regulate its development and maintenance. Here we show that the receptor for the cytokine interleukin-11 (IL-11Rα) is required specifically for normal establishment of the decidua. Females homozygous for a hypomorphic IL-11Rα allele are fertile and their blastocysts implant and elicit the decidual response. Because of reduced cell proliferation, however, only small deciduae form. Mutant deciduae degenerate progressively, and consequently embryo-derived trophoblast cells generate a network of trophoblast giant cells but fail to form a chorioallantoic placenta, indicating that the decidua is essential for normal fetoplacentation. IL-11Rα is expressed in the decidua as well as in numerous other tissues and cell types, including the ovary and lymphocytes. The differentiation state and proliferative responses of B and T-lymphocytes in mutant females were normal, and wild-type females carrying IL-11Rα mutant ovaries had normal deciduae, suggesting that the decidualization defects do not arise secondarily as a consequence of perturbed IL-11Rα signaling defects in lymphoid organs or in the ovary. Therefore, IL-11Rα signaling at the implantation site appears to be required for decidua development.     

Collection and normal levels of the amyloid precursor protein in plasma

The amyloid precursor protein is contained in plantelet alpha granules and released with degranulation. Methods are described to control for amyloid precursor protein release from platelets during blood collection and processing. In normal subjects (n = 97; age range, 44–84 years), the average plasma level of amyloid precursor protein was 6.5 ± 1.8 ng/ml.