Identification and consequences of galectin-3 expression in pituitary tumors.

Although the mechanisms regulating pituitary tumor development and progression are still unclear, new information on the molecular mechanisms involved in the pathogenesis of human pituitary tumors have accumulated. Recent evidence suggests that galectin-3 plays an important role in pituitary tumorigenesis and in tumor progression. Galectin-3 is expressed in a variety of tumors and the intensity of expression and localization depend on tumor progression, invasiveness and metastatic potential. Galectin-3 expression has been used as a potential diagnostic and/or prognostic marker in a variety of neoplasms. This review summarizes existing information regarding the structural and functional properties of galectin-3 protein as well as the LGALS3 gene in pituitary tumorigenesis. Given its role in pituitary tumor cell proliferation and in apoptosis, galectin-3 may be a target for the treatment of aggressive pituitary tumors.

The earliest pathologic alterations in dysferlinopathy.

BACKGROUND: Dysferlinopathies are associated with proximal or distal muscular dystrophy. Dysferlin immunolocalizes to the muscle fiber periphery but does not associate with the dystrophin--glycoprotein complex; its function in humans, and the mechanism by which it causes muscle fiber injury, are not known. The authors therefore searched for pathogenetic clues by examining early abnormalities in nonnecrotic muscle fibers in dysferlinopathy. Five dysferlin-deficient patients were investigated. Weakness was distal in two, proximal in one, and both proximal and distal in two. Patient 5 was only mildly affected. METHODS: Immunoblot analysis, membrane attack complex (MAC) immunolocalization, and quantitative electron microscopy. RESULTS: In Patients 1 through 4, but not in 5, part or the entire surface of isolated nonnecrotic muscle fibers immunostained for MAC. Quantitative electron microscopy of 175 nonnecrotic muscle fibers revealed one or more of the following: 1) small (0.11 to 1.8 microm) plasmalemmal defects in 64% of fibers; 2) thickened basal lamina over some defects; 3) replacement of the plasma membrane by one to multiple layers of small vesicles in 57% of fibers; 4) papillary projections, frequently disintegrating, in 24 to 36% of fibers in Patients 1 through 4 but absent in fibers of Patient 5; 5) small subsarcolemmal vacuoles, some undergoing exocytosis, in 57% of fibers; and 6) infrequent subsarcolemmal regions containing rough endoplasmic reticulum and abundant free ribosomes. CONCLUSIONS: Dysferlin is likely required for maintaining the structural integrity of the muscle fiber plasma membrane, and plasma membrane injury is an early event in the pathogenesis of dysferlinopathy. MAC activation can participate in but is not an initial or primary event causing muscle fiber injury.

Myopathy, myasthenic syndrome, and epidermolysis bullosa simplex due to plectin deficiency.

Plectin, an intermediate filament linking protein, is normally associated with the sarcolemma, nuclear membrane, and intermyofibrillar network in muscle, and with hemisdesmosomes in skin. A 20-year-old female with epidermolysis bullosa simplex since birth had progressive ocular, facial, limb, and trunkal weakness and fatigability since age 9, fivefold CK elevation, a 25% decrement with myopathic motor unit potentials and increased electrical irritability on electromyography, and no anti-acetylcholine receptor (AChR) antibodies. Plectin expression was absent in muscle and severe plectin deficiency was noted in skin. Morphologic studies revealed necrotic and regenerating fibers and a wide spectrum of ultrastructural abnormalities: large accumulations of heterochromatic and lobulated nuclei, rare apoptotic nuclei, numerous cytoplasmic and few intranuclear nemaline rods, disarrayed myofibrils, thick-filament loss, vacuolar change, and pathologic alterations in membranous organelles. Many endplates (EPs) had an abnormal configuration with chains of small regions over the fiber surface and a few displayed focal degeneration of the junctional folds. The EP AChR content was normal. In vitro electrophysiologic studies showed normal quantal release by nerve impulse, small miniature EP potentials, and fetal as well as adult AChR channels at the EP. Our findings support the notion that plectin is essential for the structural integrity of muscle and skin, and for normal neuromuscular transmission.