Quantifiable Biomarkers of Normal Aging in the Japanese Medaka Fish (Oryzias latipes)

BACKGROUND: Small laboratory fish share many anatomical and histological characteristics with other vertebrates, yet can be maintained in large numbers at low cost for lifetime studies. Here we characterize biomarkers associated with normal aging in the Japanese medaka (Oryzias latipes), a species that has been widely used in toxicology studies and has potential utility as a model organism for experimental aging research. PRINCIPAL FINDINGS: The median lifespan of medaka was approximately 22 months under laboratory conditions. We performed quantitative histological analysis of tissues from age-grouped individuals representing young adults (6 months old), mature adults (16 months old), and adults that had survived beyond the median lifespan (24 months). Livers of 24-month old individuals showed extensive morphologic changes, including spongiosis hepatis, steatosis, ballooning degeneration, inflammation, and nuclear pyknosis. There were also phagolysosomes, vacuoles, and residual bodies in parenchymal cells and congestion of sinusoidal vessels. Livers of aged individuals were characterized by increases in lipofuscin deposits and in the number of TUNEL-positive apoptotic cells. Some of these degenerative characteristics were seen, to a lesser extent, in the livers of 16-month old individuals, but not in 6-month old individuals. The basal layer of the dermis showed an age-dependent decline in the number of dividing cells and an increase in senescence-associated β-galactosidase. The hearts of aged individuals were characterized by fibrosis and lipofuscin deposition. There was also a loss of pigmented cells from the retinal epithelium. By contrast, age-associated changes were not apparent in skeletal muscle, the ocular lens, or the brain. SIGNIFICANCE: The results provide a set of markers that can be used to trace the process of normal tissue aging in medaka and to evaluate the effect of environmental stressors

Calcinosis cutis arising in morphea: a case series

Calcinosis cutis, although common in systemic sclerosis, has been rarely reported in patients with morphea. We describe four patients with calcinosis cutis arising within morphea plaques, discuss their treatments and outcomes, and review previously published cases. Current management recommendations for concomitant morphea and dystrophic calcinosis cutis are based on limited data and expert opinion, which has primarily focused on reduction of active inflammation and reduction of symptoms related to calcinosis or ulceration. In most cases, no improvement of calcinosis was noted. The use of intralesional corticosteroids to active lesions in conjunction with systemic treatment, including methotrexate when indicated, appear promising treatments to halt progression of the disease. Surgical excision seems to be the most definitive treatment for calcinosis affecting morphea plaques, but the current literature lacks details regarding disease recurrence following operative management

Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus

The earliest autoantibodies in lupus are directed against the RNA binding autoantigen Ro60, but the triggers against this evolutionarily conserved antigen remain elusive. We identified Ro60 orthologs in a subset of human skin, oral, and gut commensal bacterial species and confirmed the presence of these orthologs in patients with lupus and healthy controls. Thus, we hypothesized that commensal Ro60 orthologs may trigger autoimmunity via cross-reactivity in genetically susceptible individuals. Sera from human anti-Ro60-positive lupus patients immunoprecipitated commensal Ro60 ribonucleoproteins. Human Ro60 autoantigen-specific CD4 memory T cell clones from lupus patients were activated by skin and mucosal Ro60-containing bacteria, supporting T cell cross-reactivity in humans. Further, germ-free mice spontaneously initiated anti-human Ro60 T and B cell responses and developed glomerular immune complex deposits after monocolonization with a Ro60 ortholog-containing gut commensal, linking anti-Ro60 commensal responses in vivo with the production of human Ro60 autoantibodies and signs of autoimmunity. Together, these data support that colonization with autoantigen ortholog-producing commensal species may initiate and sustain chronic autoimmunity in genetically predisposed individuals. The concept of commensal ortholog cross-reactivity may apply more broadly to autoimmune diseases and lead to novel treatment approaches aimed at defined commensal species

Frictional Trauma/Mechanic Skin Diseases

Normal skin can resist mechanical insults to a certain degree. If not counteracted by protective measures, excessive friction or superficial skin injuries may develop into cutaneous disease. Post-traumatic eczema can persist or recur for long periods of time, while preexisting dermatoses can be aggravated by mechanical trauma. If a dynamic relationship between trauma and development of eczema is made probable, it has important medical implications when job related. Only a minor fraction of individuals exposed to repetitive mechanical stimuli such as friction develop physical irritant contact dermatitis, indicating a probable role of genetic predisposition in addition to environmental factors such as temperature and sweat production. Hyperkeratoses, calluses, and lichenification are common clinical manifestations of a frictional eczema which most often involves the hands. Frictional hand dermatitis can be caused by working in various occupations, from office workers to craftsmen such as carpet installers and shoe makers. Time from onset of exposure to development of frictional dermatitis can vary from weeks to years. Post-traumatic eczema following mechanical injury usually occurs within weeks. It may occur in association with an underlying endogenous dermatosis (isomorphic reaction of Koebner’s phenomenon) or occur as an isolated idiopathic reaction. The clinical features of posttraumatic eczema are indistinguishable from other types of hand eczema.</p

Stem cells and the ocular lens : implications for cataract research and therapy

The transparent, avascular and non-innervated ocular lens is suspended in the light path between the cornea and retina by the zonular fibres within the zonula ciliaris (also called the Zonule of Zinn; Fig. 9.1). The lens provides approximately 30% of the eye’s focussing power and, through the combined action of the ciliary muscle and zonular fibres, the lens provides all the accommodating ability of the eye, that is, the ability to change focus between near and far objects. These dual properties of transparency and accommodation cause the lens to play a vital role in the development of key motor and social functions that require good vision