Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with uncontrolled autoimmune chronic active hepatitis have increased numbers of activated T lymphocytes expressing interleukin 2 receptors (IL2R). A soluble form of IL2R has recently been described whose proposed role is to downregulate T cell activation by competing for interleukin 2. We investigated whether a deficiency of soluble IL2R could account for the high concentrations of IL2R positive T lymphocytes in autoimmune chronic active hepatitis. Soluble IL2R was measured by enzyme-linked immunosorbent assay in the serum of 16 children with autoimmune chronic active hepatitis, eight with chronic liver disease due to hepatitis B virus infection, seven with Wilson's disease, nine with alpha 1 antitrypsin deficiency, and 15 healthy age matched controls. Soluble IL2R concentration was significantly higher in patients with autoimmune chronic active hepatitis than in healthy controls (mean (SEM) 475 (75) U/ml, 145 (8) U/ml respectively, p less than 0.01). Eleven patients who had active disease had significantly higher soluble IL2R concentrations (590 (89) U/ml) than the five cases with inactive disease (220 (36) U/ml, p less than 0.01). No difference was found between the controls and the patients with chronic liver disease due to hepatitis B infection, Wilson's disease, and alpha 1 antitrypsin deficiency. Percentages and absolute numbers of surface IL2R positive T cells as detected by immunofluorescence were significantly higher in the patients with autoimmune chronic active hepatitis (11.8% (1); 274/microliters (31)) than in controls (0.2% (0.1); 5/microliters (2), p less than 0.001), the highest values being found in those with uncontrolled disease. A significantly positive correlation was observed between concentrations of soluble IL2R and the percentage of T cells expressing IL2 receptors (r=0.67, p<0.001). These results indicate that the high levels of IL2R positive T lymphocytes characteristic of autoimmune chronic active hepatitis are not due to a deficiency of soluble IL2 receptors.
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PMID:Soluble interleukin 2 receptors in autoimmune chronic active hepatitis. 237 74

The purpose of this uncontrolled, prospective study was to evaluate the influence of long-term augmentation therapy with plasma-derived alpha 1-antitrypsin (AAT) on lung function parameters in patients with severe emphysema caused by AAT deficiency. Twenty patients (mean age 48 years) received AAT infusions once weekly for up to 36 months. No adverse effects were observed. At the beginning of the study, mean (+/- SEM) FEV1 was 1.35 +/- 0.12 liters and mean TLCO was 54 +/- 4% of predicted. After 36 months of treatment, mean FEV1 was 1.25 +/- 0.12 liters (p = n.s) and the TLCO was 52 +/- 4% predicted (p = n.s). Similar values were obtained before and after therapy for FVC (2.79 +/- 0.23 vs. 2.82 +/- 0.21 liters), MEF50 (0.72 +/- 0.09 vs. 0.68 +/- 0.08 liters/s), RV (4.60 +/0 0.44 vs 4.45 +/- 0.311) and TLC (7.72 +/- 0.49 vs. 7.38 +/- 0.42 l). The calculated annual loss of FEV1 (35.6 ml/year) was smaller than in historical untreated patients with AAT deficiency.
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PMID:Long-term augmentation therapy in twenty patients with severe alpha-1-antitrypsin deficiency--three-year follow-up. 904 69

High-resolution computed tomography (HRCT) can be used to diagnose and quantify emphysema noninvasively, as significant correlations have been found between the histological grade on resected lung specimens and quantified (q) computed tomography (CT). In this study, we performed thin section qHRCT in patients with severe hereditary alpha-1-antitrypsin (AAT) deficiency. AAT deficiency is the most common genetic cause of emphysema in adults, and exercise intolerance is the most disabling, distressing consequence of emphysema for the majority of patients. qHRCT was used to quantify precisely the alterations in the lung parenchyma due to pulmonary emphysema. Up until now, the important relationship between the severity of emphysema and the reduced exercise capacity has received little attention. Therefore the purpose of the study was to investigate the relationship between emphysema as displayed by qHRCT and cardiopulmonary exercise testing (CPX) in patients with severe cardiopulmonary impairment. - qHRCT was performed in 21 patients with homozygous AAT deficiency. CT scans were obtained at three spirometrically standardized levels at the carina and (5 cm above and below the carina). The mean lung density at 50% of vital capacity and a quantitative histogram analysis of the frequencies of CT values were determined. All patients underwent symptom-limited CPX to analyse simultaneously cardiovascular and ventilatory systems responses. - In all patients, qualitative CT assessment demonstrated panlobular emphysema with large and extensive areas of uniform low attenuation, characteristically with a lower-lobe distribution. Mean CT density values of the patients (-845 +/- 6.9 (mean +/- SEM)) were significantly correlated with work capacity (r = 0.55, p <0.01), oxygen-pulse (r = 0.54, p <0.01) and functional dead space ventilation (r = -0.54, p <0.01). Moreover, severe emphysema index (CT values below a threshold value of 950 HU) correlated positively with functional dead space ventilation (r = 0.60, p <0.01) and alveolar-arterial oxygen difference (r = 0.70, p <0.001). - These results clearly demonstrate that CPX parameters, indicating a disturbed pulmonary gas exchange and a ventilation-perfusion-mismatch during exercise, are significantly related to the extent of lung emphysema.
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PMID:Relations between cardiopulmonary exercise testing and quantitative high-resolution computed tomography associated in patients with alpha-1-antitrypsin deficiency. 981 33

alpha1-Antitrypsin (AAT) deficiency predisposes to bronchitis and emphysema associated with neutrophilic airway inflammation. The efficacy of augmentation therapy has not been proven clinically or by demonstrating an effect on airway inflammation. We treated 12 patients with four infusions of Prolastin (60 mg/kg) at weekly intervals and monitored both the serum and secretion concentrations of AAT as well as markers of neutrophilic inflammation, including myeloperoxidase, elastase, and the neutrophil chemoattractants interleukin-8 and leukotriene B(4). Serum AAT rose and was maintained above the protective threshold. In addition, AAT concentrations in the sputum rose from a mean of 0.17 microM (SEM +/- 0.04) before therapy to concentrations similar to nondeficient subjects (0.43 +/- 0.12) 1 week after the first infusion (p < 0.01). This was associated with a reduction in elastase activity (p < 0.002) and the chemoattractant leukotriene B(4) (p < 0.02), which fell from a median baseline value of 13.46 nM (range, 4.17-55.00) to 8.62 nM (4.23-21.59) the day following the last infusion. Although median values for myeloperoxidase and interleukin-8 also fell, the changes failed to achieve statistical significance. In summary, short-term therapy with AAT increased lung secretion concentrations and was associated with a fall in leukotriene B(4), which is thought to be central to the airway inflammation of AAT deficiency.
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PMID:The effect of augmentation therapy on bronchial inflammation in alpha1-antitrypsin deficiency. 1204 22