Chitotriosidase activity in patients with interstitial lung diseases

BACKGROUND: In previous papers, we found significantly higher activity of chitotriosidase, a macrophage derived enzyme, in serum and BAL of patients with sarcoidosis, especially in those with progressing disease and lung involvement, than in controls. Locally and systemically produced chitotriosidase activity was correlated with radiological stage and also with degree of lung infiltration, suggesting that this enzyme may play a role in the pathogenesis of sarcoidosis and may be used as a marker of disease severity. AIM: To analyse chitotriosidase activity in serum and bronchoalveolar lavage of patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis and to compare it with chitotriosidase activity in controls and sarcoidosis patients. METHODS: Chitotriosidase activity was determined by a fluorometric assay. RESULTS: The results showed that serum chitotriosidase activity was only elevated in sarcoidosis patients; in patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with systemic sclerosis it was in the normal range. On the contrary, in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients the activity was significantly higher than in controls. CONCLUSION: Serum chitotriosidase is a potential marker of sarcoidosis severity; it increases in sarcoidosis in relation to radiological stage and degree of lung infiltration. The increase in chitotriosidase activity in BAL of sarcoidosis and idiopathic pulmonary fibrosis patients suggests that the enzyme could be involved in fibrogenesis in diffuse lung diseases. Further research is needed to understand the role of chitotriosidase in the pathogenesis of sarcoidosis and its involvement in fibrotic remodelling in certain diffuse lung diseases.     

Monitoring markers of disease activity for interstitial lung diseases with serum surfactant proteins A and D

Objectives:   Surfactant protein (SP) A and D are specific serum markers for interstitial lung diseases including idiopathic pulmonary fibrosis (IPF). The authors evaluated the critical roles of these markers on the prognoses of patients with IPF and the mechanisms of their elevation in sera.
Methodology:   The authors evaluated the relationship between prognosis and the serum markers in 82 IPF patients. The protein content and mRNA expression of the markers were evaluated using rats with interstitial pneumonia induced by bleomycin administration.
Results:   Higher levels of serum SP-D at the time of the initial visit to the Sapporo Medical University Hospital were associated with poorer prognoses, while SP-A showed no significant affect on survival. Causes of the elevation in sera were due to the acceleration of, not only production in the lungs, leakage into the circulation. The elevation was associated with alveolitis but not fibrosis.
Conclusions:   SP-D is a good predictor of the prognosis in patients with IPF.     

Blood gas changes following Priscoline administration in mitral stenosis and chronic lung diseases

The O₂ and CO₂ content in the arterial blood of normal individuals and of patients with mitral stenosis and with chronic lung disease were examined in the resting state and ten minutes after the intravenous administration of Priscoline. In about half of the normal individuals a drop in the O₂ content was observed after the drug; however, this change was statistically nonsignificant. In the majority of patients with mitral stenosis and with chronic pulmonary disease a statistically significant drop of the O₂ content was observed while changes in the CO₂ content varied. The observed drop in the arterial O₂ content after administration of a drug known to cause vasodilation and augmented cardiac output is thought to be brought about by increased perfusion of poorly ventilated areas in the lungs and/or by increased flow through true intrapulmonary shunt vessels.     

真菌毒素与肺部疾病

近年来由于广谱抗生素的大量应用、各种免疫抑制宿主的增加、侵人性操作如气管插管、呼吸道介入诊疗技术的广泛应用，真菌相关性的肺部疾病明显增加。真菌毒素是真菌的二次代谢产物，在其致病机制中起着主要作用，同时也在某些疾病的治疗方面发挥一定的积极作用。真菌种类极多，分布极广，一种真菌可以产生多种毒素，一种毒素也可以由多种菌株产生。现对常见产毒真菌、主要真菌毒素的作用机制及其与肺部疾病的关系做一简要综述。     

Cryptic proteolytic activity of dihydrolipoamide dehydrogenase

The mitochondrial enzyme, dihydrolipoamide dehydrogenase (DLD), is essential for energy metabolism across eukaryotes. Here, conditions known to destabilize the DLD homodimer enabled the mouse, pig, or human enzyme to function as a protease. A catalytic dyad (S456-E431) buried at the homodimer interface was identified. Serine protease inhibitors and an S456A or an E431A point mutation abolished the proteolytic activity, whereas other point mutations at the homodimer interface domain enhanced the proteolytic activity, causing partial or complete loss of DLD activity. In humans, mutations in the DLD homodimer interface have been linked to an atypical form of DLD deficiency. These findings reveal a previously unrecognized mechanism by which certain DLD mutations can simultaneously induce the loss of a primary metabolic activity and the gain of a moonlighting proteolytic activity. The latter could contribute to the metabolic derangement associated with DLD deficiency and represent a target for therapies of this condition.     

Neutral-alkaline proteolytic activity in rat cardiac muscle cells

Homogenates that were prepared from isolated heart muscle cells were found to have reduced ability to degrade endogenous proteins to free amino acids at alkaline pH in comparison to homogenates of whole hearts. The decrease in alkaline proteolytic activity was the result of loss from the particulate fraction. The heart muscle cell preparations retained considerable proteolytic activity at neutral-alkaline pH as indicated by the hydrolysis of [³H]acetylcasein and [¹⁴C]protein from rat heart to acid soluble products. In both cases, the decrease in activity was associated with the particulate fraction and appeared to be the result of the absence of mast cells. The extractable activity of control hearts and heart muscle cells eluted from DEAE-cellulose columns as two peaks of caseinolytic activity. The first peak eluted with 0.07 to 0.12 m NaCl and included a thiol protease. The second peak eluted with 0.25 m NaCl and was seen only in the presence of 5 mm CaCl₂. The specific activity of the Ca²⁺-dependent protease was reduced 50% in muscle cell preparations as compared to control heart.     

Blood serum immunoglobulins in thyrotoxicosis

Serum immunoglobulin content was determined in 85 patients with thyrotoxicosis and in 80 healthy persons by radial immunodiffusion in agar after Mancini by means of monospecific antisera (made at the N. F. Gamaleya Institute of Epidemiology immunoglobulins of classes G and M. The most pronounced increase was noted in patients with severe and moderate thyrotoxicosis.