六分钟步行试验后心率恢复情况可预测特发性肺纤维化患者的病死率

背景和目的:观察特发性肺纤维化(IPF)患者在6分钟步行试验(6MWT)结束后1min和2min时心率储备率,探讨该指标是否可以预测IPF患者的病死率.方法:对2003至2008年美国国市犹太医学研究中心的76例IPF患者进行肺功能评估和6MWT.     

Association of chromosome 12p genetic polymorphisms with lung adenocarcinoma risk and prognosis

The mapping near Kras2 of pulmonary adenoma susceptibility 1 (Pas1), a major locus affecting inherited predisposition to lung cancer in mice prompted us to test the homologous human region (12p12) for association with lung adenocarcinoma, by a population-based study. We genotyped 213 lung adenocarcinoma patients and 219 healthy blood donor subjects for five polymorphic markers mapping in the putative region of interest. Three marker polymorphisms, located in a region spanning approximately 700 kb, were significantly associated with lung adenocarcinoma risk. Furthermore, polymorphisms in KRAS2 and PTHLH loci were also associated with tumor prognosis. These results suggest the existence of a human Pas1 homologous locus on chromosome 12p12.      

Use of mannose ligands in IVF screens to mimic zona pellucida-induced acrosome reactions and predict fertilization success

A predictive test for determining whether motile populations of human spermatozoa will fertilize eggs in vitro has been an elusive goal of clinical research. We have developed an assay for the ability of motile human spermatozoa to bind fluorescein isothiocyanate-labelled mannosylated bovine serum albumin (Man-FITC-BSA) as a test for the presence of sperm surface receptors (lectins) for mannose ligands. Mannosylated ligands are present on the human zona pellucida and are involved in the species-specific binding of human spermatozoa to the zona pellucida. We now demonstrate in prospective blinded analysis that the fractional increase in acrosome loss following a mannose ligand challenge is highly correlated with the rate of fertilization in vitro. Using an incremental increase of acrosome exocytosis of >0.1 as a threshold to predict which specimens will yield normal fertilization, the assay has a sensitivity of 97.8%, a specificity of 83.3%, a positive predictive value of 95.7% and a negative predictive value of 90.7%. These data indicate that testing for a mannose-induced acrosome reaction may be useful in assessment of sperm function prior to in- vitro fertilization in order to assign males to conventional insemination or intracytoplasmic sperm injection protocols.      

Increased C5a receptor expression in sepsis

Excessive production of the complement activation product C5a appears to be harmful during the development of sepsis in rodents. Little is known about the role of the C5a receptor (C5aR) and its presence in different organs during sepsis. Using the cecal ligation/puncture (CLP) model in mice, we show here that C5aR immunoreactivity was strikingly increased in lung, liver, kidney, and heart early in sepsis in both control and neutrophil-depleted mice. C5aR mRNA expression in these organs was also significantly increased during sepsis. Immunohistochemical analysis revealed patterns of increased C5aR expression in parenchymal cells in all four organs following CLP. Mice injected at the start of CLP with a blocking IgG to C5aR (alphaC5aR) showed dramatically improved survival when compared with animals receiving nonspecific IgG, as did mice injected with alphaC5a. In alphaC5aR-treated mice, serum levels of IL-6 and TNF-alpha and bacterial counts in various organs were significantly reduced during CLP when compared with control CLP animals. These studies demonstrate for the first time that C5aR is upregulated in lung, liver, kidney, and heart during the early phases of sepsis and that blockade of C5aR is highly protective from the lethal outcome of sepsis.     

A randomized, controlled trial to study the efficacy and safety of C1 inhibitor concentrate in treating hereditary angioedema

BACKGROUND: No effective treatment exists in the United States for acute attacks of hereditary angioedema (HAE). STUDY DESIGN AND METHODS: To evaluate the efficacy and safety of C1 inhibitor concentrate in treating HAE, a large primary care and referral center hospital conducted a randomized, placebo-controlled, double-blind trial with intent-to-treat analysis. Of the 36 patients enrolled in the study, 23 received treatment, and 22 completed the trial. C1 inhibitor concentrate or albumin (placebo) infusions were administered in a blind fashion to HAE patients who came to the hospital for treatment no later than 5 hours after an attack began. RESULTS: Relief was almost twice as fast in persons receiving C1 inhibitor concentrate than in the controls: 7.62 hours (mean; SD 7.08) versus 15.35 hours (mean; SD 8.31), respectively. The difference for time-to-relief was highly significant (p = 0.007, Mann-Whitney U test). The median time-to-relief was 6.17 hours (interquartile range 0.33-15.35) in the treatment group and 15.35 hours (interquartile range 14.00-22.83) in the control group. Resolution of symptoms was one-third faster in the C1 inhibitor concentrate group than in the placebo group: 23.98 hours (mean; SD 14.81) and 34.58 hours (mean; SD 13.56), respectively (p = 0.09, Mann- Whitney U test). Recovery of functional C1 inhibitor was 119.65 percent (mean; SD 50.80), and half-life was 37.87 hours (mean; SD 19.75). Recovery of antigenic C1 inhibitor was 147.75 percent (mean; SD 97.68), and half-life was 24.01 hours (mean; SD 9.70). There were no viral infections or serious adverse effects from the drug after 70 attacks in the treatment group and 96 attacks in the control group. CONCLUSIONS: C1 inhibitor concentrate is a safe, effective treatment for acute attacks of HAE.     

Genetic differences in red cell osmotic fragility: analysis in allophenic mice

Mice of strain DBA/2J were found to produce red cells considerably more resistant to osmotic lysis than cells from C57BL/6J or the F1 hybrid between the two strains. Such strain-specific differences in osmotic fragility could be the result of genetically determined humoral or other systemic differences that indirectly influence red cell properties. Alternatively, this phenotypic variation might be an inherent property of the erythrocyte themselves and be directly controlled by their genotype. Analysis of red cells from allophenic (mosaic) mice of the strain composition C57BL/6J in equilibrium DBA/2J demonstrated that the latter possibility is the case. In such mice, erythrocytes of the DBA/2J genotype are relatively more resistant to osmotic lysis than are those of the C57BL/6J genotype; partial lysis of allophenic blood at intermediate salt concentrations results in marked enrichment for DBA/2J cells among the survivors. Future experiments designed to determine the mechanism underlying this difference can now focus on the properties of the red blood cells per se with the certainty that this property is inherent to the genotype of each cell.     

Functional characterization of platelet-bound factor XIa: retention of factor XIa activity on the platelet surface

Previously we have shown that both factor XI and factor XIa are bound specifically to distinct, high-affinity sites on the surface of activated platelets in the presence of high Mr kininogen. To determine the functional significance of factor XIa binding to platelets, bound factor XIa has now been compared with the unbound enzyme. Platelets incubated with thrombin, high Mr kininogen, and 125I-labeled factor XIa bound 130 to 500 molecules of factor XIa per platelet. Scatchard analysis of binding data give a dissociation constant (Kd) of 822 pmol/L +/- 140 (SEM). Rates of factor IX activation, assayed by release of trichloroacetic acid-soluble 3H-labeled activation peptide from purified [3H]-factor IX, were similar when factor XIa was bound to platelets and when it was free in solution. The platelet-bound factor XIa was isolated by centrifugation through 20% sucrose and was functionally characterized both in a factor XIa coagulation assay and in the factor IX activation peptide release assay in comparison with unbound factor XIa in the presence of treated platelets. The functional activity of platelet-bound factor XIa as a factor IX activator as well as its structural integrity were shown to be fully retained on the platelet surface. Since platelets bind factor XI and promote its proteolytic activation to factor XIa, factor XIa binding to platelets may serve to localize factor IX activation to the hemostatic plug, where factor XIa is protected from inactivation by plasma protease inhibitors and where acceleration of subsequent coagulation reactions can occur.