Long-term follow-up patients with leukemia receiving platelet transfusions: identification of a large group of patients who do not become alloimmunized

Alloimmunization is the major complication of platelet transfusion therapy in patients with acute leukemia. To evaluate whether alloimmunization continues to be a long-term problem in patients surviving induction therapy, 114 patients with acute nonlymphocytic leukemia (ANLL) who survived more than 6 mo and who received multiple courses of chemotherapy and abundant platelet transfusions were studied. Clinical response to random donor platelets and lymphocytotoxic antibody (LCTAb) were measured pretreatment and serially throughout the study period. Fourteen patients (12%) were alloimmunized upon admission, 34 (30%) patients became alloimmunized during remission induction therapy, and 66 (58%) patients did not become alloimmunized during that period. Sixty-one of these 66 patients (92%) never became alloimmunized and responded to random donor platelets during their subsequent course despite the fact they received multiple further platelet transfusions, whereas the alloimmunized patients tended to remain alloimmunized for their entire clinical course. There was no difference in age or sex between groups, and prognostic factors predicting alloimmunization could not be detected. In greater than 90% of patients not alloimmunized at admission, the presence or absence of LCTAb after induction predicts later alloantibody production. This information can be used to plan the type of platelet transfusions (HLA-matched or random donor) needed for subsequent maintenance and induction therapy. It may also help to identify a group of patients to whom more aggressive maintenance chemotherapy may be more safely administered.     

Oleamide activates peroxisome proliferator-activated receptor gamma (PPARγ) in vitro

Background

Lipid metabolism is altered in subjects with liver steatosis. FAS is a key enzyme in de novo lipogenesis and both FAS gene expression and enzymatic activity are primarily regulated by metabolic signals in the liver. Lipoprotein lipase (LPL), the rate-limiting enzyme for the hydrolysis of core triglycerides, plays a pivotal role in lipid metabolism. This study aims to investigate if circulating levels of FAS and LPL could be clinically associated with liver steatosis.

Methods

In this work, we present data obtained from a subsample of 94 subjects with liver steatosis enrolled by NUTRIEPA study, a nutritional trial in subjects with liver steatosis. Serum levels of FAS protein and LPL activity were evaluated by ELISA test and by a fluorescent method, respectively. The diagnosis and the degree of liver steatosis were based on laboratory and ecographic measurements. Statistical methods included Kruskal-Wallis analysis of variance and Wilcoxon signed-rank test, where appropriate. The ?? ² test has been performed to analyse categorical variables.

Results

The subjects with severe steatosis had significantly higher serum levels of FAS protein and LPL activity compared to subjects with mild and moderate liver steatosis. Moreover, a positive trend in serum levels of FAS expression from lower to higher degree of steatosis was also detected.

Conclusions

We describe a relationship between human liver steatosis and elevated levels of circulating lipogenic enzymes. Increased serum levels of FAS expression and LPL activity could be considered a marker of severe liver steatosis.     

Cerebrovascular accidents in infective endocarditis: role of anticoagulation

Anticoagulation is still a matter of debate in infective endocarditis,since it can increase the risk of complications, mostly neurological.In our series of 269 patients with native valve endocarditisstudied between 1970 and 1982, 35 were anticoagulated. We observed14 patients with brain infarcts, of whom five died, and 12 patientswith cerebromeningeal or brain haemorrhage of whom six died.In a similar series of 63 patients with prosthetic valve endocarditis,all of whom were on anticoagulation and were studied between1972 and 1987, we observed five patients with brain infarcts,three of whom died, and two patients with brain haemorrhage,one of whom died. The frequency of cerebrovascular accident(CVA) was similar for both groups (111% in prosthetic endocarditisvs 11.5% in native valve endocarditis, P = ns), as was mortalityrate (57% vs 48–4%, P = ns). CVA are significantly morefrequent among anticoagulated patients (19/94 vs 19/238: P<0.01),but the mortality rate in CVA is similar for anticoagulatedand non-ant icoagulated patients (11/19 vs 8/19: P = ns). Theindications for anticoagulation in infective endocarditis remainsimilar to those in valvular heart disease. In patients withinfective endocarditis, anticoagulation with heparin shouldbe maintained whenever a brain infarct is present, unless itis large and/or haemorrhagic.     

糖尿病流行病学研究中应用OGTT资料评估胰岛β细胞功能的可能性--468例非糖尿病Pima印第安人葡萄糖钳研究资料分析

目的　探讨以口服葡萄糖耐量试验 (OGTT)的简单参数在糖尿病流行病研究中评估胰岛 β细胞功能的可能性。方法　美国Pima印第安人糖耐量正常者 332例、糖耐量低减者 1 36例参与本试验。各例均做静脉葡萄糖耐量试验 (IVGTT) ,OGTT及正葡萄糖钳试验。计算Homa IR ,Homa β ,第一时相胰岛素分泌量 (AIR) ,胰岛素曲线下面积 ,ΔI30 /ΔG30 ,胰岛素介导的葡萄糖代谢率 (M ,mg·kg- 1 ·min- 1 )。从基本病理生理学概念推导新 β细胞功能指数MBCI=(FINS×FPG) / (PG2h +PG1h- 2×FPG) (FINS :空腹胰岛素 ;FPG :空腹血糖 ;PG1h和PG2h分别为OGTT 1h和 2h的血糖 )。以线性回归分析正葡萄糖钳技术测定的胰岛素敏感性与不同的β细胞功能指数的组合对血糖水平的贡献 ,探讨以OGTT的简单参数评估β细胞功能的可能性。 结果　 (1 )调整M后 ,IGT组AIR、ΔI30 /ΔG30 、Homa β和MBCI与OGTT 2h血糖水平的偏相关系数分别为 - 0 .30、- 0 .30、- 0 .2 9及 - 0 .37(P均 <0 .0 0 1 ) ,但在NGT组则分别为 - 0 .0 6(P >0 .0 5)、0 .0 1 (P >0 .0 5)、- 0 .30 (P <0 .0 0 1 )及 - 0 .43(P <0 .0 0 1 )。 (2 )以OGTT 2h血糖为因变量 ,分别以M +AIR ,M +ΔI30 /ΔG30 ,M +Homa β,M +MBCI为自变量做线性回归分析 ,显示M +MBCI能解释     

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Interleukin-3, GM-CSF, and TPA induce distinct phosphorylation events in an interleukin 3-dependent multipotential cell line

The mechanism of action of the hemopoietic growth factor, murine interleukin-3 (mIL-3), was investigated using an mIL-3-dependent multipotential hematopoietic cell line, B6SUtA1. Murine granulocyte- macrophage colony-stimulating factor (mGM-CSF) was as potent as mIL-3 in stimulating these cells. In addition, sodium orthovanadate, an inhibitor of phosphotyrosine phosphatase, and 12-O-tetradecanoyl- phorbol-13-acetate (TPA), a known activator of protein kinase C, also stimulated DNA synthesis in these cells, suggesting that protein phosphorylation might be involved in the mechanism of action of mIL-3 and mGM-CSF. To assess this possibility, intact B6SUtA1 cells exposed for brief periods to mIL-3, mGM-CSF, and TPA were analyzed for changes in phosphorylation patterns using metabolic 32P-labeling and antibodies to phosphotyrosine. Both mIL-3 and mGM-CSF induced the serine-specific phosphorylation of a 68-Kd cytosolic protein, whereas all three agents stimulated the serine-specific phosphorylation of a 68-Kd membrane protein. Furthermore, mIL-3 stimulated tyrosine phosphorylation of the 68-Kd membrane protein, as well as of 140-, 90-, 55, and 40-Kd proteins. The 90-Kd protein was also tyrosine phosphorylated in response to mGM-CSF. These phosphotyrosine containing proteins were not detected in TPA-treated cells. These results indicate that protein phosphorylations on tyrosine and serine residues occur in B6SUtA1 cells following short-term incubation with mIL-3 or mGM-CSF and that most of these phosphorylation events are mediated by kinases other than protein kinase C (PkC).     

Gastroparesis in patients with inactive Crohn's disease: a case series

Background  

Few studies have described patients with foregut dysmotility in inflammatory bowel disease. The aim of this case series was to evaluate clinical characteristics of 5 patients with inflammatory bowel disease and symptoms and signs of upper gut dysmotility.     

Transient leukemoid proliferation of the cytogenetically unbalanced +21 cell line of a constitutional mosaic boy

A newborn without any signs of Down's syndrome was found to have an acute proliferation that remitted without drug therapy. Chromosomal analysis of blood, bone marrow, and skin cells revealed that the child was a constitutional mosaic with normal cells and a low number of cells in which one no. 21 chromosome was replaced by a probably isochromosome for the no. 21 long arm: 46,XY/46,XY,i(21q). The abnormal cell line of the mosaic appeared to be selectively involved in this proliferation.     

Procoagulant activity of reversibly acylated human factor Xa

The plasma clotting factors used to treat hemophiliacs who have developed inhibitory antibodies have a shared history of limited clinical safety and utility. To improve on existing bypass factors, we have developed a reversibly acylated form of human plasma factor Xa capable of providing a time-dependent release of procoagulant activity. Factor Xa was treated with p-amidinophenyl p'-anisate to generate anisoyl Xa. The chemical modification of the protein involves acylation of the active site serine residue of factor Xa. Anisoyl Xa deacylated in a time, pH, and temperature-dependent manner. Active factor Xa generated on deacylation of anisoyl Xa exhibited amidolytic and prothrombinase complex activities in in vitro assays, the level being comparable to those of untreated factor Xa. When Anisoyl Xa was infused into rabbits, active factor Xa was generated on deacylation of the acylated enzyme, which shortened the activated partial thromboplastin time (APTT) in a dose-dependent manner. The duration of effect on rabbit APTT could be directly correlated to the level of human plasma factor Xa. Because anisoyl Xa bypasses the "tenase" complex that is compromised in hemophilia A and B and is unaffected by inhibitory antibodies, it has the potential to be used as an effective bypass therapy.