Isolation of an abnormal protein C molecule from the plasma of a patient with thrombotic diathesis

Protein C has been purified from the plasma of a patient with thrombotic diathesis. Both before and after isolation, the protein showed reduced capacity to hydrolyze synthetic substrates and to anticoagulate plasma. Proteolysis with the soluble thrombin- thrombomodulin complex proceeded normally and to completion as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Approximately one-third of the protein is functional, indicating a heterozygous defect. Indirect studies suggest that the abnormal component can bind to protein S and phospholipids. Both forms of activated protein C can also incorporate radiolabeled diisopropylfluorophosphate.     

Application of finite-element analysis with optimisation to assess thein vivo non-linear myocardial material properties using echocardiographic imaging

An application of finite-element analysis with an optimisation technique to assess the myocardial material properties in diastasisin vivo is described. Using the data collected from an animal model, the three-dimensional geometry of the left ventricular chamber, at several times in diastole, was reconstructed. From the measurement of the ventricular chamber pressure during image acquisition, finite-element analysis was performed to predict the expansion during diastasis. Initially, by restricting the motion of the epicardial nodes and computing the reaction forces, an ‘equivalent pericardial pressure’ was determined and applied in subsequent analysis. The duration of diastasis was divided into three or four intervals and the analysis was performed at each interval to assess the material properties of the myocardium. Using such a step-wise linear approach, the non-linear material properties of the myocardium during passive expansion was determined. Our results demonstrated that the computed ‘equivalent pericardial pressure’ increased with and was smaller than the corresponding left ventricularchamber pressure. The passive myocardium exhibited a linear tangent modulus against chamber pressure relationship which is equivalent to an exponential stress/strain relationship, similar to those suggested byin vitro studies.     

Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component

A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex.     

Hypersensitivity pneumonitis: evaluation with CT

Thirteen chest radiographs and computed tomographic (CT) scans obtained from 11 patients with hypersensitivity pneumonitis were reviewed. The CT findings were correlated with open lung biopsy findings in seven patients. The two patients with acute hypersensitivity pneumonitis showed air-space opacification on CT scans. An open lung biopsy, done in one of these patients, demonstrated noncaseating granulomas and filling of the air spaces with macrophages. The nine patients with subacute hypersensitivity pneumonitis showed small, rounded opacities and patchy air-space opacification on CT scans. These findings reflected the histologic findings, which consisted of interstitial pneumonitis, cellular bronchiolitis, and small, noncaseating granulomas. The six patients with symptoms for 12 months or longer also showed irregular linear opacities on CT scans, corresponding to areas of fibrosis. CT scans were superior to radiographs in helping to assess the type and extent of abnormalities, and high-resolution CT scans were superior to conventional CT scans.     

沙赛普肽注射液的细菌内毒素检测

目的：用鲎试剂检测沙赛普肽注射液中的细菌内毒素。方法：采用鲎试法（LT）与家兔法（RT）对沙赛普肽注射液进行细菌内毒素检测。结果：两种方法检查结果一致,用直接稀释法排除细菌内毒素的干扰。结论：以鲎试法用于控制沙赛普注射液的热原方法可行。     

Placental pathologic changes of maternal vascular underperfusion in bronchopulmonary dysplasia and pulmonary hypertension

Introduction

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy, and BPD-associated pulmonary hypertension (PH) is a serious complication that can negatively impact later childhood health. There is growing evidence that lung injury leading to BPD and PH is due to chronic fetal hypoxia-ischemia. The purpose of this study was to investigate whether placental pathologic changes of maternal vascular underperfusion (MVU) are associated with BPD, and further increased with PH.

Methods

We conducted a 5-year retrospective cohort study of premature infants born ≤28 weeks. BPD was defined as persistent oxygen requirement at 36 weeks corrected gestational age. PH was identified using a standardized algorithm of echocardiogram review. Archived placental slides underwent standardized masked histopathologic review. Logistic regression modeling was performed, taking into account important maternal and infant covariates.

Results

Among 283 births, 121 had MVU, of which 67 (55%) developed BPD, and 24 (20%) had PH. Among the common neonatal complications of extreme prematurity, BPD was the only outcome that was increased with MVU (P < 0.001). After adjustment for birth weight, fetal growth restriction, preeclampsia and other factors, infants with MVU were more likely to develop BPD (adjusted odds ratio = 2.6; 95% confidence interval = 1.4, 4.8). Certain MVU sublesions (fibrinoid necrosis/acute atherosis and distal villous hypoplasia/small terminal villi) were increased with PH (P < 0.001).

Discussion

Placental MVU may identify BPD infants who were exposed to intrauterine hypoxia-ischemia, which increases their risk for development of PH disease.

Conclusions

Our findings have important implications for providing earlier and more effective therapies for BPD.