metallothionein and Atrophy

1. Metallothioneins (MTs) are small metal-binding proteins. The genes that encode MT isoforms I and II are also induced by metal at transcription level. Commonly expressed in the central nervous system (CNS) their putative function is protection against reactive oxygen species (ROS), however their role may not be restricted to this sole purpose. The physiological function of MTs in the peripheral nervous system (PNS) requires further investigation. 2. Examination of phrenic nerve cross-sections from MT-I and MT-II double knockout mice (MT-I, II KO) showed a significant reduction (P=0.0032) in the mean myelinated axons calibre compared to 129/Sv wild type (Wt) counterparts. 3. Analysis of the Gaussian spectra specifically attributes this atrophy to the large myelinated class (>or=4 microm) of axon considered selectively vulnerable in motor neuron disease (MND). Supporting the results, these axons also showed increased irregularity in shape. 4. In conclusion, MTs directly or indirectly influence the radial equilibrium of large myelinated motor axons.

Topics: Animals; Atrophy; Metallothionein; Mice; Mice, Knockout; Motor Neurons; Nerve Fibers, Myelinated; Oxidative Stress; Phrenic Nerve

Dermal atrophy of more than 50% of the locoregional dermis may be the predominant histopathological feature in dermatofibroma and dermatofibrosarcoma protuberans. This may cause diagnostic difficulties. In the present study 26 cases of atrophic dermatofibroma were compared with three cases of atrophic dermatofibrosarcoma protuberans. Clinically, both conditions mostly occurred on the (upper) trunk of females. While atrophic dermatofibroma usually presented as a reddish, umbilicated lesion (0.5-1cm), often suspected to be a basal cell carcinoma, atrophic dermatofibrosarcoma protuberans showed irregularly arranged tan-brown plaques (3-6 cm). Histologically, atrophic dermatofibroma showed a regular silhouette with a smooth nodular (9/26) or scalloped lower margin with an intervening lace-like pattern of superficial fatty tissue infiltration (17/26) and variable sclerosis: atrophic dermatofibrosarcoma protuberans showed a deep, irregular infiltration of fatty tissue in a lacelike/honeycomb and/ or multilayered pattern, but no sclerosis. Immunohistochemically, atrophic dermatofibroma was mostly negative with QBEnd 10 (CD34;24/26), variably positive for factor XIIIa (20/26) and metallothionein (11/26). Labelling for factor XIIIa and metallothionein was usually seen in 'early' (metabolically active) lesions, while 'late' sclerotic ones were negative. In contrast to atrophic dermatofibroma all three atrophic dermatofibrosarcoma protuberans showed a consistently uniform profile: CD34 positive, factor XIIIa and metallothionein negative. Our study delineates atrophic dermatofibroma and atrophic dermatofibrosarcoma protuberans as distinct entities clearly distinguishable from each other by clinicopathologic criteria.

Topics: Adult; Aged; Antigens, CD; Antigens, CD34; Atrophy; Child; Dermatofibrosarcoma; Diagnosis, Differential; Female; Histiocytoma, Benign Fibrous; Humans; Immunohistochemistry; Male; Metallothionein; Middle Aged; Skin Neoplasms; Transglutaminases

Topics: Atrophy; Biopsy; Cadmium Poisoning; Humans; Infant; Kidney Tubules; Male; Metallothionein

A plasmid containing the mouse interferon-alpha 1 gene under control of the mouse metallothionein-I promoter was used for the construction of transgenic mice. Four transgenic mice (two males and two females) were obtained containing 1 to over 10 copies of the introduced DNA. Both males appeared to be sterile. One of the female mice founded a transgenic strain in which the foreign DNA was transmitted to her offspring in a Mendelian fashion. In this strain most male animals are sterile or turn sterile with time. Northern blot analysis of several tissues of these animals shows that expression of the introduced interferon gene occurs only in the testis. In some of the animals biologically active interferon could also be detected in testes homogenates. Histological examination of testis tissue shows an ongoing degeneration of spermatogenic cells leading to calcium deposits and complete atrophy of the seminiferous tubules.

Topics: Animals; Atrophy; DNA; Female; Gene Expression Regulation; Infertility, Male; Interferon Type I; Male; Metallothionein; Mice; Mice, Transgenic; Microtubule Proteins; Nucleic Acid Hybridization; Pedigree; Phosphoproteins; Plasmids; Promoter Regions, Genetic; Seminiferous Tubules; Stathmin; Testis; Transcription, Genetic