The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis. By positional cloning, we found a marked decrease in Attractin (Atrn) mRNA in the brain of the zi͞zi rat and identified zi as an 8-bp deletion at a splice donor site of Atrn. Atrn has been known to play multiple roles in regulating physiological processes that are involved in monocyte-T cell interaction, agouti-related hair pigmentation, and control of energy homeostasis. Rat Atrn gene encoded two isoforms, a secreted and a membrane form, as a result of alternative splicing. The zi mutation at the Atrn locus darkened coat color when introduced into agouti rats, as also described in mahogany (mg) mice, carrying the homozygous mutation at the Atrn locus. Transgenic rescue experiments showed that the membrane-type Atrn complemented both neurological alteration and abnormal pigmentation in zi͞zi rats, but that the secreted-type Atrn complemented neither mutant phenotype. Furthermore, we discovered that mg mice exhibited hypomyelination and vacuolation in the CNS associated with body tremor. We conclude from these results that the membrane Atrn has a critical role in normal myelination in the CNS and would provide insights into the physiology of myelination as well as the etiology of myelin diseases. T he zitter rat was found in a colony of Sprague-Dawley rats as a tremorous mutant, and subsequent genetic analysis showed that the abnormality was caused by an autosomal recessive gene, zitter (zi) (1, 2). The tremor develops spontaneously at 3 weeks of age, and flaccid paresis of the hind limb is observed at around 6 months of age (3). The main pathological findings are progressive hypomyelination and vacuolation in the central nervous system (CNS) (4). Hypomyelination is characterized by a significant decrease in the density of myelinated fibers and the number of myelin lamellae and is accompanied by aberrant or elongated myelin sheath formation (4). Vacuoles consist mainly of swollen astrocytic processes and enlargement of extracellular space as well as periaxonal spaces. The vacuoles are first detected in the pons and the outer thalamus at 3 weeks of age. With increasing age, vacuoles extend into the deep cortex, hippocampus, cervical spinal gray matter, and the granular layer and white matter of the cerebellum (5). However, the initiation of myelination and the fundamental structures of myelin sheaths are normal in the zitter rat. The biochemical components of myelin, such as myelin basic protein, proteolipid protein, and myelin-associated glycoprotein, are also normally expressed (5, 6). Therefore, the zitter rat is expected to provide useful tools for the study of axon-glia interaction and the assembly of myelin sheaths in the complex process of CNS myelination.The zi gene has been mapped to a genomic region between IL-1␤ (Il1b) and prion protein (Prnp) on rat chromosome (Chr) 3q35 (3, 7). Prnp is known as a causative gene for spongiform ence...

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Aim: Since atherosclerosis was recognized as an inflammatory disease in 1990, the infiltration of macrophages and T lymphocytes has been reported to be predominant in human atherosclerotic lesions. Although adventitis accompanying atherosclerosis was also described in many reports, it is still unclear whether T lymphocytes or B lymphocytes are predominant in the adventitis. In this study, the authors immunohistochemically investigated the correlation between the transition of infiltrating inflammatory cells in the adventitia with atherosclerosis and the type of coronary atherosclerosis. Methods: Sixty-four coronary atherosclerotic lesions from a surgical specimen and 47 autopsy cases were used for immunohistochemical study of CD45RO, CD20, CD68 and others. Atherosclerosis was classified into type , , , according to the 1995 AHA classification.

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Background: In 2015, infliximab was approved for the treatment of patients with intravenous immunoglobulin-refractory Kawasaki disease (KD) in Japan. However, limited real-world data exist on the usefulness of infliximab for acute KD patients. We conducted a postmarketing surveillance study in patients with acute KD refractory to conventional therapies to evaluate the safety (including any live vaccine-related infections) and the effectiveness of infliximab. Methods: This was a multicenter, prospective, open-label, single-cohort, observational study in patients with acute KD refractory to conventional therapy who were prescribed a single 5 mg/kg dose of infliximab. Safety and effectiveness of infliximab were evaluated at 1 month, and live vaccine-related infections were further observed until 6 months from KD onset. Effectiveness assessments included fever resolution rate, the incidence of coronary artery lesions and change in coronary diameter Z scores. Results: A total of 291 patients were enrolled, and all patients completed the study. Adverse drug reactions and serious adverse drug reactions were reported in 12.4% and 3.1% of patients, respectively. Live vaccine-related infections were not observed. In the 208 patients with effectiveness assessments, the fever resolution rate within 48 hours after infliximab infusion was 77.4% (95% confidence interval: 71.1–82.9). Median time until fever resolution was 16.6 hours. After infliximab administration, the incidence (at baseline: 10.9%; at the final observation point: 12.0%; maximum value: 14.6%) and severity of coronary artery lesions did not change notably. Conclusions: In this study, Infliximab for patients with acute KD refractory to conventional therapies was well tolerated and effective.