Influence of 2,3-diphosphoglycerate on the rate of oxidation of hemoglobin to methemoglobin

Summary 2,3-diphosphoglycerate, favoring the deoxyconfiguration of the hemoglobin molecule, accelerates the oxidation of hemoglobin to methemoglobin by potassiumferricyanide both in hemolysates from adult and cord blood. Hemoglobin oxidation is less enhanced in cord blood hemolysates.Supported by Deutsche Forschungsgemeinschaft (SFB 51). B.U. will present extended data to the Medical Faculty, University of Munich, as doctoral thesis.     

Effect of ASCO/CAP Guidelines for Determining ER Status on Molecular Subtype

Background

Determination of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status is standard for predicting prognosis and determining treatment options for patients with breast cancer. In 2010, the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) issued guidelines that tumors with ≥1 % positively staining cells should be considered ER positive. Here, we determined how this cutoff relates to molecular subtype.

Methods

Clinicopathological characteristics were compared between ER-negative, ER-positive, and low-ER-staining (1–10 %) tumors using chi-square analysis with P < 0.05 defining statistical significance. Gene expression data were generated for 26 low-ER-staining tumors, and their intrinsic subtype determined. Immunohistochemistry (IHC)-defined surrogate subtypes, using the threshold of positivity defined by ASCO/CAP guidelines, were compared with molecular subtypes.

Results

Low-ER-staining tumors were clinicopathologically more similar to ER-negative than to ER-positive tumors; 88 % of low-staining tumors were basal like or HER2 enriched. Only those tumors expressing 10 % ER-positive cells were classified as luminal A subtype.

Conclusions

Under ASCO/CAP guidelines, tumors with 1–10 % ER staining would be classified as ER positive, yet most are basal like or HER2 enriched and have pathological features similar to ER-negative tumors. Clinical trials seeking to treat tumors of ER-negative basal-like and/or HER2-enriched subtypes should thus not preclude enrollment based solely on results of ER immunohistochemistry. As ER status is a critical element in the choice of treatments for patients with breast cancer, it is imperative that the most effective method for classifying tumors be developed.     

可溶性抗HAV抗体Fab片段的原核表达

0　引言　甲型肝炎病毒 (HAV)是危害人类健康的致病原之一 ,目前已有多种用于接触前预防的甲肝疫苗 ;但对于接触后预防或短期到 HAV高流行区的旅游者的预防 ,则多采用免疫球蛋白作被动免疫 .在接触后 (14d内 )和潜伏期早期 ,注射免疫球蛋白预防甲肝的有效率达 85 %左右 .血源性免疫球蛋白虽然效价高 ,应用效果好 ,但可能被血源病原体污染 .因此基因工程人源抗体有望成为接触后预防的首选制剂 .我们从人源噬菌体抗体组合文库中筛选到一株甲肝特异性抗体 [1 ] ,在此基础上构建了可溶性表达载体 ,并获得可溶性表达 ,为该抗体的进一步研究打…     

Adrenocortical steroids in small-for-gestational-age term infants during the early neonatal period

We evaluated adrenocortical steroid concentrations at birth and during postnatal adaptation (2 h until 7 days) in 10 vaginally delivered term small-for-gestational-age (SGA) infants and 12 term appropriate-for-gestational age infants. Plasma aldosterone, 11-deoxycorticosterone, corticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone were longitudinally measured by specific RIA after Sephadex LH-20 chromatography. Mean aldosterone was significantly higher in SGA than in appropriate-for-gestational-age infants (2 h to 7 days; p less than 0.001). In SGA infants, cortisone and cortisol levels were significantly lower in umbilical artery (p less than 0.05), and all glucocorticoid levels were significantly lower 12 h after birth (p less than 0.05). Thereafter (24 h to 7 days), only 11-deoxycortisol levels remained significantly lower in SGA; corticosterone and cortisol levels were even higher (p less than 0.05) in SGA 24 h after birth. The data suggest that SGA infants maintain high aldosterone levels throughout the 1st wk of life. Low cortisol and cortisone levels in umbilical artery as well as low glucocorticoid levels at 2 h and/or 12 h compared to term appropriate-for-gestational-age infants may reflect either a less stressful postnatal adaptation or, more likely, a reduced adrenocortical synthesis in term SGA infants.     

Leukocyte and endothelial activation in a laboratory model of extracorporeal membrane oxygenation (ECMO)

An inflammatory response and a capillary leak syndrome frequently develop during the treatment of neonatal respiratory failure by extracorporeal membrane oxygenation (ECMO). The present study was performed to investigate leukocyte activation and endothelial cell dysfunction that are associated with prolonged contact of blood components with synthetic surfaces. Laboratory ECMO was performed with fresh human blood at 37 degrees C for 8 h (n = 6). Leukocyte activation was measured by L-selectin (CD62L) and CD18 integrin surface expression and by neutrophil-derived elastase release. To monitor endothelial activation, endothelial cell ICAM-1 (CD54) expression was measured in cultured endothelial cells from human umbilical veins (HUVEC) after incubation with plasma from the ECMO experiments. CD18 integrin expression was found significantly up-regulated on polymorphonuclear neutrophils and monocytes after 2-4 h of laboratory ECMO. L-selectin was reduced on both cell types during the total duration of the experiments. Soluble L-selectin (sCD62L) and total and differential leukocyte counts remained unchanged during the experiment. Neutrophil-derived elastase content was maximal after 8 h of ECMO. Plasma from the ECMO experiments did not induce ICAM-1 expression of cultured HUVEC. We conclude that prolonged contact with synthetic surfaces during ECMO activates phagocytes, which may contribute to the inflammatory response seen in ECMO-treated patients. Activated phagocytes do not accumulate in the extracorporeal system nor release humoral factors inducing ICAM-1 expression on endothelial cells.