[Disorders of the origin of the suspensory ligament in the horse: a diagnostic challenge]

Lameness in horses due to pain originating from the proximal metacarpal/metatarsal region remains a diagnostic challenge. In cases of obvious lameness the pain can be localised to this region by diagnostic anaesthesia. Because a variety of disorders can cause lameness in this region different imaging modalities including radiography, ultrasonography and scintigraphy should be used to arrive at an accurate diagnosis. Even though a precise anatomic-pathologic diagnosis can still be an enigma, because not only bone and joints, but also soft tissue structures including the proximal suspensory ligament, its origin at the proximal metacarpus/ metatarsus, its fascia, the superficial fascia, as well as the intermetacarpal/metatarsal ligaments, the accessory ligament of the deep digital flexor tendon and both digital flexor tendons may be involved. Magnet resonance tomography (MRT) shows a high diagnostic sensitivity in imaging soft tissue structures and bone. In horses MRT is still at the beginning. The MRT appearance of the proximal metacarpal/metatarsal region has not yet been evaluated in detail and there are only few anatomic studies of the origin of the suspensory ligament in horses. The first experiences showed, that more gross and histologic examinations are necessary to fully interpret MRT-images and to differentiate pathologic alterations from clinically not relevant variations.

A common origin of the 4143insA ADAMTS13 mutation

Severely deficient activity of the von Willebrand Factor (VWF) cleaving metalloprotease, ADAMTS13, is associated with thrombotic thrombocytopenic purpura (TTP). The mutation spectrum ofADAMTS13 is rather heterogeneous, and numerous mutations spread across the gene have been described in association with congenital TTP. The 4143insA mutation is unusual with respect to its geographic concentration. Following the initial report from Germany in which the 4143insA mutation was detected in four apparently unrelated families, we have now identified this mutation in a further eleven patients from Norway, Sweden, Poland, Germany, the Czech Republic and Australia. Confirmation that the Australian patient is of German ancestry, together with the Northern and Central European origin of most of the other patients, suggests that the 4143insA mutation has a common genetic background. We established ADAMTS13 haplotypes by analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA were identical in all informative families. Three novel candidate mutations, C347S, P671L and R1060W, as well as the known mutation R507Q, were also identified during the course of the study. We conclude that 4143insA has a common genetic background and is frequent among patients with hereditary ADAMTS13 deficiency in Northern and Central European countries.

Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin

Factor V (FV) present in platelet alpha-granules has a significant but incompletely understood role in hemostasis. This report demonstrates that a fraction of platelets express very high levels of surface-bound, alpha-granule FV on simultaneous activation with 2 agonists, thrombin and convulxin, an activator of the collagen receptor glycoprotein VI. This subpopulation of activated platelets represents 30.7% +/- 4.7% of the total population and is referred to as convulxin and thrombin-induced-FV (COAT-FV) platelets. COAT-FV platelets are also observed on activation with thrombin plus collagen types I, V, or VI, but not with type III. No single agonist examined was able to produce COAT-FV platelets, although ionophore A23187 in conjunction with either thrombin or convulxin did generate this population. COAT-FV platelets bound annexin-V, indicating exposure of aminophospholipids and were enriched in young platelets as identified by the binding of thiazole orange. The functional significance of COAT-FV platelets was investigated by demonstrating that factor Xa preferentially bound to COAT-FV platelets, that COAT-FV platelets had more FV activity than either thrombin or A23187-activated platelets, and that COAT-FV platelets were capable of generating more prothrombinase activity than any other physiologic agonist examined. Microparticle production by dual stimulation with thrombin and convulxin was less than that observed with A23187, indicating that microparticles were not responsible for all the activities observed. These data demonstrate a new procoagulant component produced from dual stimulation of platelets with thrombin and collagen. COAT-FV platelets may explain the unique role of alpha-granule FV and the hemostatic effectiveness of young platelets. (Blood. 2000;95:1694-1702)

Origin of renal myofibroblasts in the model of unilateral ureter obstruction in the rat

Tubulo-interstitial fibrosis is a constant feature of chronic renal failure and it is suspected to contribute importantly to the deterioration of renal function. In the fibrotic kidney there exists, besides normal fibroblasts, a large population of myofibroblasts, which are supposedly responsible for the increased production of intercellular matrix. It has been proposed that myofibroblasts in chronic renal failure originate from the transformation of tubular cells via epithelial-mesenchymal transition (EMT) or from infiltration by bone marrow-derived precursors. Little attention has been paid to the possibility of a transformation of resident fibroblasts into myofibroblasts in renal fibrosis. Therefore we examined the fate of resident fibroblasts in the initial phase of renal fibrosis in the classical model of unilateral ureter obstruction (UUO) in the rat. Rats were perfusion-fixed on days 1, 2, 3 and 4 after ligature of the right ureter. Starting from 1 day of UUO an increasing expression of alpha-smooth muscle actin (alphaSMA) in resident fibroblasts was revealed by immunofluorescence and confirmed by the observation of bundles of microfilaments and webs of intermediate filaments in the electron microscope. Inversely, there was a decreased expression of 5'-nucleotidase (5'NT), a marker of renal cortical fibroblasts. The RER became more voluminous, suggesting an increased synthesis of matrix. Intercellular junctions, a characteristic feature of myofibroblasts, became more frequent. The mitotic activity in fibroblasts was strongly increased. Renal tubules underwent severe regressive changes but the cells retained their epithelial characteristics and there was no sign of EMT. In conclusion, after ureter ligature, resident peritubular fibroblasts proliferated and they showed progressive alterations, suggesting a transformation in myofibroblasts. Thus the resident fibroblasts likely play a central role in fibrosis in that model.

Spinal MRI supporting myelopathic origin of early symptoms in unsuspected cobalamin deficiency

We report two patients with subjectively progressive sensory symptoms and gait disturbance due to cobalamin deficiency, but only slight or absent abnormalities on neurological examination. In both patients, spinal MRI provided evidence for a myelopathic origin of the symptoms, disclosing characteristic T(2) hyperintense signal alterations confined to the posterior columns of the cervical and thoracic spinal cord. The patients illustrate the early clinical presentation of subacute combined degeneration (SCD) with a sensory neuropathy starting with acroparesthesia and Lhermitte's sign. Furthermore, the diagnostic value of spinal MRI for early diagnosis of SCD with characteristic findings is highlighted.

Occurrence and Origin of Placer Gold in Montana

From time immemorial man has used gold as a medium of exchange, a mea­sure of value, as jewelry and for ornamentation. Placer gold has led dir­ectly or indirectly to the settlement of lands, California and Alaska being the two best known examples. It has led the way to the discovery of other important mineral wealth, the discovery of the copper and silver deposits at Butte, Montana and the discovery of the silver deposits at Cripple Creek, Colorado being two good examples.

A Study on the Origin of Banded Agate

Agate in any of its varieties presents numerous problems in regard to its origin. Many types have been described and their beauty elaborated upon, but little has been written concerning their formation and the problems involved. The genesis of agate implicates an amazing complexity of physical and colloid­al chemistry, as well as, various principles of geology.