Jean Lambert Pasteels

Selenium deficiency-induced growth retardation is associated with an impaired bone metabolism and osteopenia.

Although the importance of selenium for bone metabolism is unknown, some clinical conditions such as Kashin‐Beck osteoarthropathy have been associated with selenium deficiency. Although selenium deficiency induces growth retardation in rats, it has not been established whether this growth inhibition is associated with changes in bone metabolism. We investigated the effect of selenium deficiency on bone metabolism in growing male rats fed a selenium‐deficient diet for two generations (Se−). In Se− rats, erythrocyte glutathione peroxidase activity and plasma selenium concentration were strongly reduced compared with pair‐fed selenium‐adequate rats (Se+). Weight and tail length were reduced by 31% and 13% in the Se− rats, respectively (p < 0.001). The Se− diet was associated with a 68% reduction of pituitary growth hormone (GH; p = 0.01) and a 50% reduction of plasma insulin‐like growth factor I (IGF‐I; p < 0.001). Plasma calcium was lower and urinary calcium concentration was greater in Se− rats. This group had a 2‐fold increase in parathyroid hormone (PTH) and 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] in plasma. Plasma osteocalcin and urinary deoxypyridoline were reduced by 25% and 57% in the Se− rats (p < 0.001). Selenium deficiency resulted in a 23% and 21% reduction in bone mineral density (BMD) of the femur and tibia (p < 0.001) and this effect persisted after adjustment for weight in a linear regression model. A 43% reduction in trabecular bone volume of the femoral metaphysis (p < 0.001) was found in Se− rats. This experimental study shows that growth retardation induced by selenium deficiency is associated with impaired bone metabolism and osteopenia in second‐generation selenium‐deficient rats.

Idiopathic carpal tunnel syndrome: Histologic study of flexor tendon synovium

The histologic lesions in flexor tendon synovium of 21 patients seen initially with idiopathic carpal tunnel syndrome have been studied. The findings were similar in all biopsy specimens and were typical of a connective tissue undergoing degeneration under repeated mechanical stresses.

Calbindin in vertebrate classes: immunohistochemical localization and Western blot analysis.

Calbindin immunoreactivity was investigated in various vertebrates. Positive labeling was observed in the absorptive cells of the duodenum of all birds and reptiles but not in mammals, amphibia, or fish. Staining was present in the kidney distal convoluted tubule from amphibia and higher vertebrates. Fish kidney was negative. In the central nervous system of all species investigated, cellular bodies and fibers were Calbindin positive. Their distribution was quite broad and correlates well with the previously reported mapping for chick and rat. Western blot analysis revealed two Calbindins in brain from mammals, birds, reptiles, and amphibia (27,000 and 29,000 Da). Only one band was detected in fish. We conclude that Calbindin from the evolutionary point of view is primarily a neuronal protein, with a highly conservative character.

Rat brain synthesizes two ‘vitamin D-dependent’ calcium-binding proteins

Two proteins from rat brain reacting against anti-chick intestinal vitamin D-dependent calcium-binding protein were characterized in terms of their mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and their molecular size. The proteins were present in the isolated cytoplasm and were produced following translation of brain mRNA in the rabbit reticulocyte lysate system. Their apparent molecular weight was 29,000 and 27,000 daltons whereas rat kidney contained only one protein cross-reacting with this antiserum and with a molecular weight of 27,000 daltons.

Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines

Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.

Vitamin D-dependent calcium binding protein immunoreactivity in human retina.

Using immunohistochemistry, vitamin D-dependent calcium binding protein (D-CaBP) has been detected in human retina. In the photoreceptor layer the cones are positive but the rods are negative. In the inner nuclear layer, horizontal cells and some bipolar cells are D-CaBP. In the ganglion cell layer both small and large somata are immunoreactive for D-CaBP. Beaded fibres from the outer plexiform, inner plexiform and fibre layers are also positive.

Correlations between clinical presentations of adult trigger digits and histologic aspects of the A1 pulley.

PURPOSE We aimed to report by light microscopy the normal histology of the A1 pulley, describe the histologic abnormalities of A1 pulleys in trigger digits, and look for possible correlations between these findings and the severity of the disease. METHODS In a series of 104 trigger digits operated on in 80 adult patients, the A1 pulleys were removed and histologically studied. The findings were compared with 55 normal A1 pulleys obtained from fresh-frozen cadaveric specimens. RESULTS The normal A1 pulley was composed of 3 layers: layer I, an inner, avascular, concave unicellular or bicellular gliding layer containing cartilage-like cells; layer II, a middle layer, also avascular, characterized by spindle-shaped fibroblasts; and layer III, an outer, richly vascularized layer, continuous with the membranous tendons sheath. We used a 3-grade classification, increasing in severity, to describe the histologic abnormalities observed in trigger digit A1 pulleys. Mild abnormalities (grade 1) were those with a fibrocartilaginous gliding surface almost intact. The margin between the fibrocartilaginous and membranous portions of the pulley was well delineated. In moderate abnormalities (grade 2), the avascular fibrocartilaginous gliding surface appeared fissured and thinner. The inner layer (I) was interrupted and replaced by fibrous tissue, with fissures that did not cross through the middle layer (II). A mild vascular network hyperplasia was observed in the outer layer (III), which began to invade the fibrocartilage. In severe abnormalities (grade 3), the fibrocartilaginous gliding surface was thin, discontinuous, or even completely destroyed. The vascular network hyperplasia became excessive and reached the synovial space of the flexor tendon sheath. The histologic features were correlated with the severity of the clinical symptoms (p < .001). CONCLUSIONS The histologic abnormalities observed in the A1 pulley of trigger digits are characteristic and not related to inflammation. As the trigger digit worsens, the gliding surface begins to wear and is gradually replaced by a secondary invasive hyperplasia from the outer layer. These abnormalities could be caused by a modification or an increase of the mechanical stresses along the flexor tendons.

Radiological and Histological Improvement of Oxalate Osteopathy After Combined Liver-Kidney Transplantation in Primary Hyperoxaluria Type 1

A 15-year-old patient with severe bone disease (with bilateral fractures of hips and shoulders) due to primary hyperoxaluria type 1 (PH1) was treated with combined liver-kidney transplantation after a 4-year hemodialysis period. Normalization of excessive oxalate synthesis brought in by the liver graft combined with the slow excretion of skeletal oxalate stores by the renal graft led to progressive improvement of clinical, radiological, and histological evidence of oxalate osteopathy. This allowed bilateral hip replacement 3 years after transplantation, which led to complete physical rehabilitation of the crippled patient. Combined liver-kidney transplantation constitutes the treatment of choice for end-stage renal failure due to PH1, even in the face of severe oxalate bone disease.

Ultrastructural localization of brain vitamin D-dependent calcium binding proteins

Rat brain vitamin D-dependent calcium-binding protein (D-CaBP) was assessed for vitamin D dependency, calcium binding and ultrastructural localization within neurons. No evidence of vitamin D dependency could be derived from the experiments on vitamin D-deficient rats. A 95% pure extract of the 27-kDa brain D-CaBP was shown to bind 45Ca on nitrocellulose membrane after sodium dodecyl sulphate-electrophoresis, specifically on the 27-kDa CaBP band. Immunogold staining with electron microscopy allowed detection of D-CaBP into Purkinje cells and climbing fibers of the cerebellum. The immunoreactivity was found to be hyaloplasmic and never membrane-bound. It was present in neuronal soma, neurites and postsynaptic as well as presynaptic terminals. These findings rule out D-CaBP as a possible neurotransmitter and bring further support to the hypothesis that the protein functions as a cytosolic calcium buffer. Immunohistochemical detection of D-CaBP is proposed as a means for morphologic detection of neurons with high calcium metabolism.

Computer-assisted analysis of epiluminescence microscopy images of pigmented skin lesions.

BACKGROUND Epiluminescence microscopy (ELM) is a noninvasive clinical tool recently developed for the diagnosis of pigmented skin lesions (PSLs), with the aim of improving melanoma screening strategies. However, the complexity of the ELM grading protocol means that considerable expertise is required for differential diagnosis. In this paper we propose a computer-based tool able to screen ELM images of PSLs in order to aid clinicians in the detection of lesion patterns useful for differential diagnosis. METHODS The method proposed is based on the supervised classification of pixels of digitized ELM images, and leads to the construction of classes of pixels used for image segmentation. This process has two major phases, i.e., a learning phase, where several hundred pixels are used in order to train and validate a classification model, and an application step, which consists of a massive classification of billions of pixels (i.e., the full image) by means of the rules obtained in the first phase. RESULTS Our results show that the proposed method is suitable for lesion-from-background extraction, for complete image segmentation into several typical diagnostic patterns, and for artifact rejection. Hence, our prototype has the potential to assist in distinguishing lesion patterns which are associated with diagnostic information such as diffuse pigmentation, dark globules (black dots and brown globules), and the gray-blue veil. CONCLUSIONS The system proposed in this paper can be considered as a tool to assist in PSL diagnosis.