다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

/pdf/diagnostic-criteria-for-multiple-sclerosis-2010-revisions-to-24iph50480.pdf

Diagnostic criteria for multiple sclerosis: 2010 Revisions to the McDonald criteria

Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most instances, sporadic and autosomal dominant familial ALS (FALS) are clinically similar. We have previously shown that in some but not all FALS pedigrees the disease is linked to a genetic defect on chromosome 21q (refs 8, 9). Here we report tight genetic linkage between FALS and a gene that encodes a cytosolic, Cu/Zn-binding superoxide dismutase (SOD1), a homodimeric metalloenzyme that catalyzes the dismutation of the toxic superoxide anion O2.- to O2 and H2O2 (ref. 10). Given this linkage and the potential role of free radical toxicity in other neurodenegerative disorders, we investigated SOD1 as a candidate gene in FALS. We identified 11 different SOD1 missense mutations in 13 different FALS families.

Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis

Superantigen presenting capacity of human astrocytes.

Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis (MS). The major circulating metabolite of vitamin D (25OHD) is converted to the active form (calcitriol) by the hydroxylase enzyme CYP27B1. In MS lesions the tyrosine kinase MerTK expressed by microglia and macrophages regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. We show that calcitriol downregulates MerTK mRNA and protein expression in adult human microglia and monocyte-derived macrophages, thereby inhibiting myelin phagocytosis and apoptotic cell clearance. Proinflammatory myeloid cells express high levels of CYP27B1 compared to homeostatic (TGFβ-treated) myeloid cells. Only proinflammatory cells in the presence of TNF-α generate calcitriol from 25OHD, resulting in repression of MerTK expression and function. The selective production of calcitriol in proinflammatory myeloid cells leading to downregulation of MerTK-mediated phagocytosis has the potential to reduce the risk for auto-antigen presentation while retaining the phagocytic ability of homeostatic myeloid cells, thereby contributing to inflammation reduction and enhanced tissue repair.

/pdf/vitamin-d-regulates-mertk-dependent-phagocytosis-in-human-2pv0iaizv9.pdf

Vitamin D regulates MerTK-dependent phagocytosis in human myeloid cells

Isolation and Culture of Primary Human CNS Neural Cells

Three interferon-β (IFNβ) preparations are approved for the treatment of MS: two throughout the world (Betaferon; Schering AG, Berlin, Germany, and Avonex; Biogen, Cambridge, MA) and one outside the United States (Rebif; Ares-Serono, Geneva, Switzerland). Controversy persists regarding the relation of therapeutic efficacy of the different IFNβ-1a and IFNβ-1b products. Direct comparison of different clinical trials is problematic because of their variation in design and control groups, and differences in type, dose, and route of IFN administration.

One approach to clarifying the relation of the biologic and therapeutic efficacy of IFN is to monitor induction of one or more of the scores of IFN-responsive genes, which hopefully will correlate with clinical efficacy. In this issue of Neurology , Deisenhammer et al.1 compared the capacity of the three clinically approved IFNβ preparations to induce MxA, an anti-myxovirus protein (anti-influenza), in vitro and in vivo. Compared to other genes, such as β2-microglobulin, …

Injecting rationale into interferon-β therapy

Publisher Summary This chapter focuses on the relationship between the clinical phenotypes of multiple sclerosis (MS) and their underlying immunobiologic and neurobiologic substrates. It also explains the results of or predicting outcomes of past, current, and future clinical trials in the context of the underlying disease process. It is noted that the insights into immunobiology have been derived from pathologic analyses of MS tissues, in vivo imaging, largely using magnetic resonance (MR) techniques, and animal models. The results of clinical trials conducted on well-defined subtypes of MS provide further insights and identify new challenges regarding the biologic substrates that underlie the various phases of the MS disease process. Furthermore, this chapter describes therapies involved in MS. The therapies can be immune system directed and those that are directed at the nervous system. The immune system therapies are aimed at halting disease development or progression. The therapies targeting the nervous system are aimed at protecting tissue from injury, promoting recovery, or enhancing function.

Jack P. Antel

Papers

Superantigen presenting capacity of human astrocytes.

Vitamin D regulates MerTK-dependent phagocytosis in human myeloid cells

Isolation and Culture of Primary Human CNS Neural Cells

Injecting rationale into interferon-β therapy

Multiple Sclerosis: Therapy