Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis

The aim of this study was to investigate the relationship between the biochemical markers of arthritis and the radiographic grading of osteoarthritis (OA) in knees. Seventy-one women aged 49–85 years with knee OA were studied. Anterior–posterior knee radiographs and hand radiographs were taken in all patients. The radiographic grading of OA in the knee was performed by using the Kellgren–Lawrence criteria and the joint space width. The 71 patients with knee OA were divided into two groups: 37 patients exhibiting generalized osteoarthritis (GOA) and 34 non-GOA patients, according to the grading of their hand radiograph. C-reactive protein (CRP), urinary pyridinoline, YKL-40, plasma matrix metalloproteinase (MMP)-3, MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were measured as the biochemical markers of arthritis. The radiographic grading with the Kellgren–Lawrence scale revealed a significant relationship to the joint space width (P = 0.003): the joint space width decreased with increasing Kellgren–Lawrence grade. All biochemical markers had negative correlations with the joint space width, but only urinary pyridinoline had a significant correlation (P = 0.039). Pyridinoline (P = 0.034) and TIMP-1 (P = 0.017) also exhibited a significant relationship to the Kellgren–Lawrence grade. In GOA evaluations, the joint space width did not differ between GOA and non-GOA patients. CRP, pyridinoline, YKL-40 and MMP-3 levels were significantly greater in GOA patients than in non-GOA patients. CRP, pyridinoline, YKL-40, MMP-3 and TIMP-1 levels each related to at least one of the radiographic gradings. Furthermore, pyridinoline related to every type of radiographic grading examined in the present study

Yeast Eps15-like endocytic protein Pan1p regulates the interaction between endocytic vesicles, endosomes and the actin cytoskeleton

The actin cytoskeleton plays important roles in the formation and internalization of endocytic vesicles. In yeast, endocytic vesicles move towards early endosomes along actin cables, however, the molecular machinery regulating interaction between endocytic vesicles and actin cables is poorly understood. The Eps15-like protein Pan1p plays a key role in actin-mediated endocytosis and is negatively regulated by Ark1 and Prk1 kinases. Here we show that pan1 mutated to prevent phosphorylation at all 18 threonines, pan1-18TA, displayed almost the same endocytic defect as ark1Δ prk1Δ cells, and contained abnormal actin concentrations including several endocytic compartments. Early endosomes were highly localized in the actin concentrations and displayed movement along actin cables. The dephosphorylated form of Pan1p also caused stable associations between endocytic vesicles and actin cables, and between endocytic vesicles and endosomes. Thus Pan1 phosphorylation is part of a novel mechanism that regulates endocytic compartment interactions with each other and with actin cables

Hardness Perception Based on Dynamic Stiffness in Tapping

A human can judge the hardness of an object based on the damped natural vibration caused by tapping the surface of the object using a fingertip. In this study, we investigated the influence of the dynamic characteristics of vibrations on the hardness perceived by tapping. Subjectively reported hardness values were related to the dynamic stiffness of several objects. The dynamic stiffness, which characterizes the impulsive response of an object, was acquired across the 40–1,000 Hz frequency range for cuboids of 14 types of materials by administering a hammering test. We performed two psychophysical experiments—a ranking task and a magnitude-estimation tasks—wherein participants rated the perceived hardness of each block by tapping it with a finger. We found that the perceptual effect of dynamic stiffness depends on the frequency. Its effect displayed a peak around 300 Hz and decreased or disappeared at higher frequencies, at which human perceptual capabilities are limited. The acquired results help design hardness experienced by products

Super responder of critical COVID-19 case

This report presents a case of a 74-year-old man who showed dramatic therapeutic response to treatment of coronavirus infectious disease-19 (COVID-19) pneumonia. He reported four-day history of sustained fever and acute progressive dyspnea. He developed severe respiratory failure, underwent urgent endotracheal intubation and showed marked elevation of inflammatory and coagulation markers such as c-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH) and D-dimer. Chest computed tomography (CT) demonstrated diffuse consolidation and ground glass opacity (GGO). We diagnosed critical COVID-19 pneumonia with detailed sick contact history and naso-pharyngeal swab of a reverse-transcriptase-polymerase-chain reaction (RT-PCR) assay testing. He received anti-viral drug, anti-interleukin (IL-6) receptor antagonist and intravenous methylprednisolone. After commencing combined intensive therapy, he showed dramatic improvement of clinical condition, serum biomarkers and radiological findings. Early diagnosis and rapid critical care management may provide meaningful clinical benefit even if severe case

Allelotypes of lung adenocarcinomas featuring ALK fusion demonstrate fewer onco- and suppressor gene changes

BACKGROUND: A subset of lung adenocarcinomas harboring an EML4-ALK fusion gene resulting in dominant oncogenic activity has emerged as a target for specific therapy. EML4-ALK fusion confers a characteristic histology and is detected more frequently in never or light smokers and younger patients. METHODS: To gain insights into etiology and carcinogenic mechanisms we conducted analyses to compare allelotypes of 35 ALK fusion-positive and 95 -negative tumours using single nucleotide polymorphism (SNP) arrays and especially designed software which enabled precise global genomic profiling. RESULTS: Overall aberration numbers (gains + losses) of chromosomal alterations were 8.42 and 9.56 in tumours with and without ALK fusion, respectively, the difference not being statistically significant, although patterns of gain and loss were distinct. Interestingly, among selected genomic regions, oncogene-related examples such as 1p34.3(MYCL1), 7q11.2(EGFR), 7p21.1, 8q24.21(MYC), 16p13.3, 17q12(ERBB2) and 17q25.1 showed significantly less gain. Also, changes in tumour suppressor gene-related regions, such as 9p21.3 (CDKN2A) 9p23-24.1 (PTPRD), 13q14.2 (RB1), were significantly fewer in tumours with ALK fusion. CONCLUSION: Global genomic comparison with SNP arrays showed tumours with ALK fusion to have fewer alterations in oncogenes and suppressor genes despite a similar overall aberration frequency, suggesting very strong oncogenic potency of ALK activation by gene fusion

Clinical characteristics of DM-PM ILD

Background : Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. Methodology :We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. Result : We identified 52 patients, of whom30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p<0.001), and LDH (r=0.910, p<0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p<0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p<0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p<0.001). Conclusion : ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort

Clinical characteristics of DM-PM ILD

Background : Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. Methodology :We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. Result : We identified 52 patients, of whom30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p<0.001), and LDH (r=0.910, p<0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p<0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p<0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p<0.001). Conclusion : ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort