Identification of urinary dipeptidase as the released form of renal dipeptidase

Beckwith-Wiedemann syndrome (BWS) comprises of a number of childhood abnormalities, often associated with one or more tumors. Thirty-eight patients were investigated to determine clinical and/or biological signs associated with a tumor presence. Our patients exhibited a higher incidence of tumor development (21%) than that previously reported, underlying the care with which such patients should be followed, when particular clinical features are observed: visceromegaly affecting three organs (liver, kidney, spleen), and also family history with sign of BWS such as macroglossia, omphalocele, hemihypertrophy, embryonic tumor), high body weight at birth (> or = +2 standard deviations and diastasis recti.     

Lipopolysaccharide-stimulated osteoclastogenesis is mediated by tumor necrosis factor via its P55 receptor

Chronic bone infection, as attends periodontitis, is often complicated by severe osteolysis. While LPS is believed to be central to the pathogenesis of the osteolytic lesion, the mechanisms by which this bacteria-derived molecule promotes bone resorption are unknown. We find that LPS induces bone marrow macrophages (BMMs) to express c-src, a protooncogene product that we demonstrate is a specific marker of commitment to the osteoclast phenotype. We next turned to possible soluble mediators of LPS-induced c-src. Of a number of osteoclastogenic cytokines tested, only TNF-alpha mirrors the c-src-enhancing effect of LPS. Suggesting that LPS augmentation of c-src is TNF-mediated, endotoxin sequentially induces BMM expression of TNF, followed by c-src. TNF and c-src expression, by cultured BMMs derived from LPS-injected mice, reflects duration of exposure to circulating endotoxin, intimating that endotoxin's effect in vivo is also mediated by TNF. Consistent with these findings, thalidomide (which antagonizes TNF action) attenuates c-src induction by LPS. An anti-TNF antibody blocks LPS enhancement of c-src mRNA, validating the cytokine's modulating role in vitro. Using BMMs of TNF receptor-deleted mice, we demonstrate that TNF induction of c-src is transmitted through the cytokine's p55, but not p75, receptor. Most importantly, LPS administered to wild-type mice prompts osteoclast precursor differentiation, manifest by profound osteoclastogenesis in marrow cultured ex vivo, and by a profusion of marrow-residing cells expressing the osteoclast marker tartrate resistant acid phosphatase, in vivo. In contrast, LPS does not substantially enhance osteoclast proliferation in mice lacking the p55TNF receptor, confirming that LPS-induced osteoclastogenesis is mediated by TNF in vivo via this receptor. Thus, therapy targeting TNF and/or its p55 receptor presents itself as a means of preventing the osteolysis of chronic bacterial infection.     

Cornea stress test--evaluation of corneal endothelial function in vivo by contact lens induced stress

Changes in the NHS have supported the idea of targeting health services to those in greatest need. This has meant that health visitors are increasingly having to identify 'vulnerable' families in need of increased health visiting intervention. This paper reports on a qualitative study undertaken in order to explore the ways in which health visitors plan and organize their work in relation to the concept of vulnerability. Focus groups and semi-structured interviews were carried out with health visitors from two separate geographical areas, one an inner city area and the other suburban, in order to explore the criteria by which health visitors define vulnerability and decide to increase their levels of intervention to particular families. It was found that vulnerability was extremely difficult to define but that the health visitors used criteria which were appropriate to the particular localities in which they worked to identify vulnerable families and to increase their levels of intervention to those families. Health visitors were targeting their services within a framework of a basic minimum service to all and were assessing the health needs of individuals or families rather than planning their work on the basis of community or practice profiles.     

Hereditary motor and sensory neuropathies. Clinical and molecular genetic aspects

Hereditary motor sensory neuropathies are a heterogeneous group of inherited diseases of the peripheral nerves. In this review the clinical and genetic differences between the sub-groups of this disease will be discussed. Since the discovery of a 1.5 mb duplication on chromosome 17 p11.2-12 in most patients with a hereditary motor sensory neuropathy and a variety of different mutations on chromosomes 1 and X in other patients with a similar disease profile, Dycks' clinical classification needs to be re-evaluated. In this review Dycks' taxonomy of heridihary neuropathies will be compared to a new genetic classification and a relevant diagnostic procedure proposed when a hereditary neuropathy is suspected.     

Using airborne laser scanning to monitor tree migration in the boreal-alpine transition zone

The boreal tree line is expected to advance upwards into the mountains and northwards into the tundra due to global warming. The major objective of this study was to find out if it is possible to use high-resolution airborne laser scanner data to detect very small trees — the pioneers that are pushing the tree line up into the mountains and out onto the tundra. The study was conducted in a sub-alpine/alpine environment in southeast Norway. A total of 342 small trees of Norway spruce, Scots pine, and downy birch with tree heights ranging from 0.11 to 5.20 m were precisely georeferenced and measured in field. Laser data were collected with a pulse density of 7.7 m^− 2. Three different terrain models were used to process the airborne laser point cloud in order to assess the effects of different pre-processing parameters on small tree detection. Greater than 91% of all trees > 1 m tall registered positive laser height values regardless of terrain model. For smaller trees (< 1 m), positive height values were found in 5-73% of the cases, depending on the terrain model considered. For this group of trees, the highest rate of trees with positive height values was found for spruce. The more smoothed the terrain model was, the larger the portion of the trees that had positive laser height values. The accuracy of tree height derived from the laser data indicated a systematic underestimation of true tree height by 0.40 to 1.01 m. The standard deviation for the differences between laser-derived and field-measured tree heights was 0.11-0.73 m. Commission errors, i.e., the detection of terrain objects — rocks, hummocks — as trees, increased significantly as terrain smoothing increased. Thus, if no classification of objects into classes like small trees and terrain objects is possible, many non-tree objects with a positive height value cannot be separated from those actually being trees. In a monitoring context, i.e., repeated measurements over time, we argue that most other objects like terrain structures, rocks, and hummocks will remain stable over time while the trees will change as they grow and new trees are established. Thus, this study indicates that, given a high laser pulse density and a certain density of newly established trees, it would be possible to detect a sufficient portion of newly established trees over a 10 years period to claim that tree migration is taking place.     

Percutaneous nephrostolithotomy. What is its role in 1997?

A fully automated isocratic high-performance liquid chromatographic method for the determination of 9-cis-retinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid and 4-oxo-all-trans-retinoic acid, has been developed using on-line solid-phase extraction and a column switching technique allowing clean-up and pre-concentration in a single step. A 500-microliter sample of serum was diluted with 750 microliters of a solution containing 20% acetonitrile and the internal standard 9,10-dimethylanthracene. About 1000 microliters of this mixture was injected on a 20 x 4.6 mm I.D. poly ether ether ketone (PEEK) pre-column with titanium frits packed with Bondapak C18, 37-53 microns, 300 A particles. Proteins and very polar compounds were washed out to waste, from the pre-column, with 0.05% trifluoroacetic acid (TFA)-acetonitrile (8.5:1.5, v/v). More than 200 aliquots of diluted serum could be injected on this pre-column before elevated back-pressure enforces replacement. Components retained on the pre-column were backflushed to the analytical column for separation and detection at 360 nm. Baseline separation was achieved using a single 250 x 4.6 mm I.D. Suplex pKb-100 column and a mobile phase containing 69:10:2:16:3 (v/v) of acetonitrile-methanol-n-butanol-2% ammonium acetate-glacial acetic acid. A total time of analysis of less than 30 min, including sample preparation, was achieved. Recoveries were in the range of 79-86%. The limit of detection was 1-7 ng/ml serum and the precision, in the concentration range 20-1000 ng/ml, was between 1.3 and 4.5% for all five compounds. The method was applied for the analysis of human serum after oral administration of 60 mg Roaccutan. The method is well suited for pharmacological studies, while the endogenous levels of some retinoic acid isomers are below the limit of quantitation.     

Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system

Currently in vivo gene delivery by synthetic vectors is hindered by the limited diffusibility of complexes in extra-cellular fluids and matrices. Here we show that certain formulations of plasmid DNA with linear polyethylenimine (22 kDa PEI, ExGene 500) can produce complexes that are sufficiently small and stable in physiological fluids so as to provide high diffusibility. When plasmid DNA was formulated with 22 kDa PEI in 5% glucose, it produced a homogeneous population of complexes with mean diameters ranging from 30 to 100 nm according to the amount of PEI used. In contrast, formulation in physiological saline produced complexes an order of magnitude greater (> or = 1 micron). Intraventricular injection of complexes formulated in glu-cose showed the complexes to be highly diffusible in the cerebrospinal fluid of newborn and adult mice, diffusing from a single site of injection throughout the entire brain ventricular spaces. Transfection efficiency was followed by histochemistry of beta-galactosidase activity and double immunocytochemistry was used to identify the cells transfected. Transgene expression was found in both neurons and glia adjacent to ventricular spaces. Thus, this method of formulation is promising for in vivo work and may well be adaptable to other vectors and physiological models.