Expression of embryonic zeta-globin and epsilon-globin chains in a 10- year-old girl with congenital anemia

A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia.     

Heterogeneity in human prothrombin: analysis of cause

Two fractions of human prothrombin can be isolated from single donor plasma by the technique of heparin-agarose chromatography in (sodium) citrate buffer, pH 7.5, as previously reported for pooled plasma. The two fractions, designated H-II1 and H-II2, are found in a ratio of approximately 4:1. Both forms comigrate in sodium dodecyl sulfate gel electrophoresis; however, under nondenaturing electrophoretic conditions, each fraction migrates as a discrete entity with a different mobility. The larger fraction (H-II1) has a faster mobility towards the anode. Isoelectric focusing in urea of H-II1 reveals that it has two components, a minor component with a pl of 5.25 (H-II1a) and a major component with a pl of 5.40 (H-II1b). H-II2 has a pl of 5.6 H- II1 and H-II2 possess the same amino terminal residue (alanine, 0.87- 0.92 mole/mole) and the same number of gamma -carboxyglutamic acid residues (9.8-10.5). Their amino acid composition is indistinguishable. However, the two fractions of prothrombin differ in their content of neutral sugar and of sialic acid residues. Removal of sialic acid with neuraminidase abolishes the electrophoretic heterogeneity. Thus, the charge heterogneity of the three variants of prothrombin found in normal human plasma appears to result exclusively from differences in the number of sialic acid residues attached to the protein moiety of the molecule.     

Hematopoietic supportive functions of mouse bone marrow and fetal liver microenvironment: dissection of granulocyte, B-lymphocyte, and hematopoietic progenitor support at the stroma cell clone level

We dissected the functions of the microenvironment of bone marrow (BM) and fetal liver (FL) at the cellular level by cloning individual stromal calls and characterizing their phenotypical and functional features. Stromal cell clones derived from FL are large in size (mean forward light scatter intensity [mFSC] of 450), express the surface antigen Thy-1 but not Sca-1 and 6 out of 6 are able to differentiate into fat accumulating adipocytes. BM derived stromal cell clones are either small (mFSC of 250) or large (mFSC of 450), express Sca-1 but not Thy-1 and only 2 out of 7 differentiate towards adipocytes. Heterogeneity in terms of vascular adhesion molecule-1, intracellular adhesion molecule-1 and heat stable antigen expression was found among the different cell clones. Functional assays using long- and short-term cocultures of stromal and hematopoietic calls revealed: (1) the capacity of 8 out of 12 stromal cell clones to support the expansion of primitive hematopoietic progenitors (colony forming unit spleen day 12) more than 10 weeks. Fat accumulation but not expression of stem cell factor by stromal cells did correlate with this supportive function. (2) Better support of granulocyte maturation and proliferation by BM- compared to FL-derived stromal cell clones. However, stromal cell clones from both organs expressed macrophage-colony stimulating factor. (3) The ability of 4 out of 12 stromal cell clones (derived from both, FL and BM) to support the expansion of Interleukin-7 dependent pre-B cells from the BM. Pre-B cell growth stimulating factor was not restricted to supporters. (4) Mutual exclusiveness of myeloid and lymphoid support in that a given stromal cell clone supported either pre B-cell or granulocyte expansion. Experiments comparing the support of BM- and FL-derived hematopoietic progenitors showed identical responses of late (B220+/c-kit-) but strikingly different responses of early (B220+/c-kit+) pre-B cells, revealing different proliferation requirements for FL- versus BM- derived early pre-B cells in vitro.     

Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line

BACKGROUND & AIMS: Helicobacter pylori uniquely colonizes the human stomach and produces gastric mucosal inflammation. High-output nitric oxide production by inducible nitric oxide synthase (iNOS) is associated with immune activation and tissue injury. Because mononuclear cells comprise a major part of the cellular inflammatory response to H. pylori infection, the ability of H. pylori to induce iNOS in macrophages was assessed. METHODS: H. pylori preparations were added to RAW 264.7 murine macrophages, and iNOS expression was assessed by Northern blot analysis, enzyme activity assay, and NO2- release. RESULTS: Both whole H. pylori and French press lysates induced concentration-dependent NO2- production, with peak levels 20-fold above control. These findings were paralleled by marked increases in iNOS messenger RNA and enzyme activity levels. iNOS expression was synergistically increased with interferon gamma, indicating that the H. pylori effect can be amplified by other macrophage-activating factors. Studies of lipopolysaccharide (LPS) content and polymyxin B inhibition of LPS suggested that the H. pylori effect was attributable to both LPS- dependent and -independent mechanisms. CONCLUSIONS: iNOS expression in macrophages is activated by highly stable H. pylori products and may play an important role in the pathogenesis of H. pylori-associated gastric mucosal disease. (Gastroenterology 1996 Dec;111(6):1524-33)     

Expression of tissue factor and factor VIIa/tissue factor inhibitor activity in endotoxin or phorbol ester stimulated U937 monocyte-like cells

Previously, unstimulated cells of the human monocytic tumor cell line U937 have been shown to possess a negligible cell-surface tissue factor (TF) activity, and to secrete a small amount of factor VIIa/tissue factor (VIIa/TF) inhibitor activity. On stimulation with endotoxin or with phorbol myristate acetate (PMA), TF of these cells is known to be increased approximately fourfold. In this report, we demonstrate that VIIa/TF inhibitor is also increased on stimulation of U937 cells with endotoxin (approximately equal to threefold) or with PMA (approximately equal to 20-fold). Notably, the secretion of the inhibitor persisted after the cell surface TF had started to decline. Further, when serum- free media from PMA stimulated cells was electrophoresed on a sodium dodecyl sulfate (SDS) gel, we eluted two inhibitor activity peaks corresponding to Mr approximately equal to 47,000 and Mr approximately equal to 36,000. The molecular weights of these peaks are similar to those obtained earlier from human plasma for this inhibitor(s).     

可验证的剪应变溃疡病因理论和胃溃疡发生机制

建立一个合乎逻辑的科学的消化性溃疡病因理论,以反映溃疡病在现实中所有的问题．归纳在现实中与胃溃疡相关的事物,循证演绎溃疡形成的过程．溃疡发生的原因是剪应变．胃溃疡的发生是当胃壁回缩时,凸向胃腔内的高张力皱褶,直接或间接地作用在高张力机体组织的同一个位置上,长时间的挤压或频繁地冲压碾磨超过极限,黏膜肌层被剪切,发生了剪应变,造成肌层缺损成溃疡．溃疡病的发生是正常生理组织和生理功能,在一定条件下产生的结果．源于现实的溃疡剪应变理论,可以在实践中得到检验．     

Clinically occult, noncalcified breast cancer: serial radiologic- pathologic correlation in 27 cases

A serial radiographic-pathologic correlation based on specimen radiography was performed on 27 consecutive, clinically occult, noncalcified breast cancers to determine the frequency of and correlation between appearances at mammography, pathologic diagnoses, and the features of the histologic margins. Twenty (74%) of the lesions were infiltrating ductal cancers, five (19%) were intraductal cancers, and two (7%) were medullary cancers. Forty-one percent of these malignancies contained microscopic calcifications. Lesions demonstrated at mammography in these 27 cases consisted of a well-defined round mass (n = 1); well-defined lobulated masses (n = 2); indistinct round, oval, or lobulated masses (n = 7); irregular or mixed lesions (n = 7); spiculated masses (n = 9); and architectural distortion (n = 1). Histologic margins of infiltrating and intraductal cancers, created by several types of tumor-fat interfaces and surrounding reactive fibrosis, correlated with these radiographic appearances. Serial specimen radiographic-pathologic correlation can improve our understanding of the appearance of early breast cancer at mammography.