Soluble CD26 is inversely Associated with Disease Severity in Patients with Chronic Eosinophilic Pneumonia

Backgrounds: CD26, a multifunctional T cell surface glycoprotein, is a type II transmembrane protein containing only six amino acid residues in its cytoplasmic region. In addition to its membrane form, CD26 exists in plasma in a soluble form (sCD26), which is thought to be the extracellular domain of the molecule cleaved from the cell surface. Recent studies indicated CD26 have an important role in the pathogenesis of asthma, known as Th2 like disease. The function of CD26 in the esosinophlic lung disease is not well understood.Methods: Serum sCD26 was determined by enzyme-linked Immunosorbent assay in patients with acute eosinophilic pneumonia, chronic eosinophilic pneumonia (CEP), and sarcoidosis, and in healthy volunteers, to establish its value for discriminating between disease entities and as marker of disease activity.Results: Soluble CD26 was signifi cantly reduced in CEP and was related to disease severity. In particular, sCD26 was inversely correlated with arterial oxygen tension in CEP.Conclusion: Serum levels of sCD26 might appear to be useful as a new marker of CEP disease activity

Relationship between White Matter Lesions and Progression of Cognitive Decline in Alzheimer's Disease

Background: This study examined the relationship between baseline white matter lesions (WMLs) and the progression of cognitive decline in patients with late-onset Alzheimer's disease (AD). Methods: Fifty-six patients with AD were included in the study (23 men, 33 women; mean age, 77.8 years). All subjects were treated with acetylcholinesterase inhibitors and followed up for approximately 1 year. The Mini-Mental State Examination (MMSE) score was assessed at least twice to evaluate the progressive cognitive impairment. All subjects underwent brain MRI at baseline and were divided into WMLs(-), mild WMLs(+), and moderate WMLs(+) groups based on WML severity. Changes in MMSE scores between baseline and follow-up were analyzed using the Wilcoxon signed-rank test. Results: MMSE scores at baseline did not differ significantly among the three groups (p = 0.1658), whereas MMSE scores at the follow-up evaluation were significantly lower in the moderate WMLs(+) group than in the WMLs(-) group (p = 0.0257). The mean MMSE scores remained above baseline values during the approximately 1-year follow-up in the WMLs(-) group, whereas they were decreased in the mild and moderate WMLs(+) groups. Moreover, the frequency of improvement in patients from the WMLs(-) group tended to be higher than that in patients from the WMLs(+) groups. Conclusion: Baseline WMLs may be associated with the heterogeneous progression of cognitive decline in patients with AD

インスリン様成長因子-1(IGF-1)は実験的クロロキン誘発縁取り空胞ミオパチーの筋線維における空胞の過剰形成を抑制する（英語）

Objective: We investigated the effect of insulin-like growth factor-1 (IGF-1) on the histological (e.g., rimmed vacuoles and muscle fiber atrophy) and molecular properties of the denervated muscles of chloroquine-treated rats. Methods: The left hind-legs of adult male Wistar rats were denervated by ligation of the sciatic nerve.The rats with and without chloroquine treatment were given saline or IGF-1 intraperitoneally at a daily dose of either 2 or 8 mg/kg for 8 days. Results: In the denervated soleus muscles from chloroquine-treated rats, the number of rimmed vacuoles was significantly reduced in response to either low- or high-dose IGF-1. IGF-1 administration did not affect the muscle fiber atrophy. Although proteasome and ubiquitin immunostaining, and the mRNA levels of muscle-specific ubiquitin ligases and autophagy-related genes were significantly increased in denervated muscles from both rats, those levels did not change in response to either low or high-doses of IGF-1. Conclusion: IGF-1 suppressed rimmemd vacuolar formation in muscle fibers in an animal model of chloroquine-induced myopathy.　　目的：脱神経処理したクロロキン投与ラット筋の病理所見および筋崩壊に関与する分子に対するIGF-1の影響を検討した。 　方法：予め左側の坐骨神経を結紮（脱神経）したラットにクロロキン、または生理的食塩水（生食水）を各々投与した（各20匹）。そのうち両ラットの各10匹に連日IGF（2 mg/kg、8 mg/kg、各5匹）を投与し、残りの各10匹にIGF-1の代わりに同量の生食水を8日間、腹腔内に注射した。 　結果：クロロキン投与ラットの脱神経したヒラメ筋でのみ多数の縁取り空胞（rimmed vacuole）を認め、少量および大量のIGF-1投与によりrimmed vacuoleを有する筋線維数は有意に減少した。IGF-1は筋線維の萎縮には効果はなかった。プロテアソームおよびユビキチンの免疫染色、筋特異的ユビキチンリガーゼおよびオートファジー関連遺伝子のmRNAレベルはクロロキン投与および非投与（生食水投与）の脱神経筋で有意に増加したが、少量および大量のIGF-1投与ではいずれも有意な変化はなかった。 　結論：IGF-1は、クロロキン誘発ミオパチーの動物モデルの筋萎縮は抑制しないが、筋線維内のrimmed vacuoleの形成を抑制する

Incidence of myeloperoxidase anti-neutrophil cytoplasmic antibody positivity and microscopic polyangitis in the course of idiopathic pulmonary fibrosis

SummaryBackgroundPulmonary fibrosis is a manifestation of microscopic polyangitis (MPA), and often precedes the detection of MPA. The prevalence and sequence of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and MPA in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) have not been precisely elucidated.MethodsWe enrolled 61 consecutive patients with IPF and measured the MPO-ANCA titers at initial presentation and during the follow-up period. Clinical, radiologic and histologic features of MPO-ANCA-positive cases were examined.ResultsOf 61 patients, 3 (4.9%) had positive MPO-ANCA titers at the initial presentation of IPF. During the disease course, MPO-ANCA-positive conversion occurred in 6 patients and the prevalence of ANCA increased to 14.8%. Among the nine patients positive for MPO-ANCA, two patients developed MPA during follow-up. Histologic features of MPO-ANCA-positive pulmonary fibrosis were compatible with the usual interstitial pneumonia pattern in which alveolar hemorrhage and capillaritis were not observed. The patients with MPO-ANCA-positive conversion showed increased percentages of bronchoalveolar lavage eosinophils and more frequent complication of pulmonary emphysema compared to those with MPO-ANCA-negative IPF.ConclusionsThe findings of the present study demonstrated that patients with an initial diagnosis of IPF occasionally acquire MPO-ANCA, which develops to MPA during the disease course of IPF. The presence of pulmonary eosinophilia and low attenuation areas on computed tomography scans might be predictive of MPO-ANCA positive conversion