Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 2-day-old girl developed a severe lactic acidosis with a normal lactate/pyruvate ratio and hyperammonaemia. Plasma arginine and citrulline levels were below the limit of detection. In muscle total pyruvate dehydrogenase complex (PDHC) and pyruvate decarboxylase (E1) activities were reduced to a fraction of lower control values. The acute neonatal period was bridged with peritoneal dialysis, dichloroacetate therapy, supplements of arginine and branched chain amino acids, a complete vitamin B complex and lipoic acid. Lactate homeostasis responded to pharmacological supplements of lipoic acid. At age 1 year the child was hypotonic, showed severe developmental retardation, optic atrophy and cranial dysmorphism. She died aged 1 year 8 months with signs of respiratory paralysis but with normal lactate levels under assisted breathing. Pathological findings at autopsy were suggestive of Leigh syndrome, interstitial pneumonia and extensive fatty infiltration of hepatocytes. Regression analysis of data from 187 plasma amino acid determinations from the patient over a period of 1 year 8 months revealed a persistent-imbalance involving alanine, glutamic acid, glutamine, proline, citrulline and branched chain amino acids. Aspects of acute and long-term therapy in this patient and some implications of the imbalances in plasma amino acids are discussed.
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PMID:Neonatal pyruvate dehydrogenase deficiency with lipoate responsive lactic acidaemia and hyperammonaemia. 250 Oct 97

Human surfactant protein C (hSP-C(1-197)) is synthesized as a 197 amino acid proprotein and cleaved to a mature 3.7 kD form. Although interstitial lung disease in patients with mutations of the hSP-C gene is becoming increasingly recognized, the mechanisms linking molecular events with clinical pathogenesis are not fully defined. We describe a full-term infant with respiratory insufficiency associated with a spontaneous heterozygous mutation resulting in a substitution of lysine for glutamic acid at position 66 (= E66K) of the proximal hSP-C COOH flanking propeptide. Lung histology and biochemical studies of the index patient (hSP-C(E66K)) revealed nonspecific interstitial pneumonia, increased alveolar total phospholipid lacking phosphatidylglycerol, and increased surfactant protein A. Localization of proSP-C from lung sections prepared from this patient using immunofluorescence and immunogold electron microscopy revealed abnormal proSP-C staining in endosomal-like vesicles of type II cells distinct from SP-B. To evaluate the effect of the E66K substitution on intracellular trafficking of proSP-C, fusion proteins consisting of enhanced green fluorescent protein (EGFP) and hSP-C(1-197) (wild type) or mutant hSP-C(E66K) were generated and transfected into A549 cells. EGFP/hSP-C(1-197) was expressed within CD-63-positive, EEA-1-negative vesicles, whereas EGFP/hSP-C(E66K) localized to EEA-1 positive vesicles. The E66K substitution is representative of a new class of SP-C mutation associated with interstitial lung disease that is diverted from the normal biosynthetic pathway. We propose that, similar to other storage disorders, lung injury results from induction of a toxic gain of function induced by the mutant product that is subject to genetic modifiers and environmental influences.
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PMID:Nonspecific interstitial pneumonia, alveolar proteinosis, and abnormal proprotein trafficking resulting from a spontaneous mutation in the surfactant protein C gene. 1555 12

Accurate and automated lung field (LF) segmentation in high-resolution computed tomography (HRCT) is highly challenged by the presence of pathologies affecting lung borders, also affecting the performance of computer-aided diagnosis (CAD) schemes. In this work, a two-dimensional LF segmentation algorithm adapted to interstitial pneumonia (IP) patterns is presented. The algorithm employs k-means clustering followed by a filling operation to obtain an initial LF order estimate. The final LF border is obtained by an iterative support vector machine neighborhood labeling of border pixels based on gray level and wavelet coefficient statistics features. A second feature set based on gray level averaging and gradient features was also investigated to evaluate its effect on segmentation performance of the proposed method. The proposed method is evaluated on a dataset of 22 HRCT cases spanning a range of IP patterns such as ground glass, reticular, and honeycombing. The accuracy of the method is assessed using area overlap and shape differentiation metrics (d(mean), d(rms), and d(max)), by comparing automatically derived lung borders to manually traced ones, and further compared to a gray level thresholding-based (GLT-based) method. Accuracy of the methods evaluated is also compared to interobserver variability. The proposed method incorporating gray level and wavelet coefficient statistics demonstrated the highest segmentation accuracy, averaged over left and right LFs (overlap=0.954, d(mean)=1.080 mm, d(rms)=1.407 mm, and d(max)=4.944 mm), which is statistically significant (two-tailed student's t test for paired data, p<0.0083) with respect to all metrics considered as compared to the proposed method incorporating gray level averaging and gradient features (overlap=0.918, d(mean)=2.354 mm, d(rms)=3.711 mm, and d(max)=14.412 mm) and the GLT-based method (overlap=0.897, d(mean)=3.618 mm, d(rms)=5.007 mm, and d(max)=16.893 mm). The performance of the three segmentation methods, although decreased as IP pattern severity level (mild, moderate, and severe) was increased, did not demonstrate statistically significant difference (two-tailed student's t test for unpaired data, p>0.0167 for all metrics considered). Finally, the accuracy of the proposed method, based on gray level and wavelet coefficient statistics ranges within interobserver variability. The proposed segmentation method could be used as an initial stage of a CAD scheme for IP patterns.
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PMID:Texture classification-based segmentation of lung affected by interstitial pneumonia in high-resolution CT. 1917 88