The beta-globin gene on the Chinese delta beta-thalassemia chromosome carries a promoter mutation

A new type of delta beta-thalassemia characterized by decreased expression of the beta-globin gene and increased expression of both G gamma and A gamma globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant beta-globin gene from this delta beta- thalassemia chromosome. An A to G transversion is identified in the "ATA" sequence of the promoter region that leads to decreased expression of the beta-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese beta-thalassemia genes where it is present on chromosomes of the same haplotype as that of the delta beta-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the delta beta-thalassemia phenotype.     

脑内注射白细胞介素-1β对淋巴结细胞应激免疫抑制因子生成的影响

our previous work showed that a suppressive factor( a protein with largemolecular weight in serum was induced by restraint stress in mice and rats,which suppressed Con Ainduced lymphocyte proliferation.It was also found that the generation of serum suppressive factorwas under control of the central nervous system.Our further study showed thatintracerebroventricular(icv )injection of interleukin 1 receptor antagonist(IL-1Ra)antagonised thegeneration of serum suppressive factor induced by restraint stress and icv injection of interleukin-1β(IL-1β)increased the generation of the suppressive factor.Our experiment also showed that the serumsuppressive factor induced by restraint stress was first made in lymph tissue and then released intoblood.The present work was designed to investigate the role of IL-1 in the brain in generation of thesuppressive factor in lymph node in mice.Icv injection of IL-1β( 1 pg/mouse) was shown tosignificantly increase the generation of the suppressive factor in lymph node.Icv injection of IL-1Ra,however ,antagonised generation of the suppressive factor.In mice without restraint stress,both thesuppressive factor in serum and in lymph node were found to be induced in dose-dependent manner byicv injection of IL-1β.Taken together,these results suggest that IL-1β in brain played a veryimportant role in generation of the suppressive factor in lymph node.The positive correlation betweenthe suppressive action of lymph node and of serum added to the evidence that lymph tissue is probablythe source of the serum suppressive factor.     

结直肠癌淋巴管生成与淋巴结转移相关检测的临床研究进展

结直肠癌是人类常见的可经淋巴道转移的恶性肿瘤,其淋巴管生成与转移过程中牵涉了多种生物标志物表达水平的改变,检测这些相关生物标志物可为结直肠癌的诊断、治疗和预后情况提供重大参考价值．本文主要综述近年来与结直肠癌淋巴管生成与淋巴结转移相关检测的临床研究进展．     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.     

Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1 (ICAM)-1) expression and neutrophil adhesion.

The acute host response to gastrointestinal infection with invasive bacteria is characterized by an accumulation of neutrophils in the lamina propria, and neutrophil transmigration to the luminal side of the crypts. Intestinal epithelial cells play an important role in the recruitment of inflammatory cells to the site of infection through the secretion of chemokines. However, little is known regarding the expression, by epithelial cells, of molecules that are involved in interactions between the epithelium and neutrophils following bacterial invasion. We report herein that expression of ICAM-1 on human colon epithelial cell lines, and on human enterocytes in an in vivo model system, is upregulated following infection with invasive bacteria. Increased ICAM-1 expression in the early period (4-9 h) after infection appeared to result mainly from a direct interaction between invaded bacteria and host epithelial cells since it co-localized to cells invaded by bacteria, and the release of soluble factors by epithelial cells played only a minor role in mediating increased ICAM-1 expression. Furthermore, ICAM-1 was expressed on the apical side of polarized intestinal epithelial cells, and increased expression was accompanied by increased neutrophil adhesion to these cells. ICAM-1 expression by intestinal epithelial cells following infection with invasive bacteria may function to maintain neutrophils that have transmigrated through the epithelium in close contact with the intestinal epithelium, thereby reducing further invasion of the mucosa by invading pathogens.     

Severe hemolytic anemia due to multiple red cell alloantibodies after an ABO-incompatible allogeneic bone marrow transplant

BACKGROUND: A patient who received an ABO-incompatible allogeneic bone marrow transplant experienced three episodes of immune hemolytic anemia due to multiple red cell (RBC) alloantibodies. CASE REPORT: A 41-year- old man with chronic myeloid leukemia received an ABO-incompatible bone marrow graft from his HLA-identical brother. Selective removal of RBCs from donor marrow before transfusion was performed by centrifugation using a continuous-flow blood cell separator. The patient was given group O Rh-positive RBCs and group A Rh-positive platelets. Prophylaxis for graft-versus-host disease consisted of cyclosporine and methotrexate. The patient experienced three hemolytic episodes, on Days 21, 35, and 160 which were due to different RBC alloantibodies (anti-K, anti-Jk(b), anti-M, IgG anti-A) produced by host lymphocytes surviving the conditioning regimen. RESULTS: The patient was group O, Jk(b-), and the marrow donor was group A, Jk(b+). After the first hemolytic episode (Day 21), immunohematologic studies showed group O RBCs and a positive direct antiglobulin test (IgG+, C3d+). Antibody screening test and eluate studies detected anti-M, anti-Jk(b), and anti-K. During the second hemolytic episode (Day 35), the patient's blood group showed a mixed population of group A and group O RBCs. The direct antiglobulin test was positive (IgG+, C3d+). Anti-M, anti-Jk(b), and IgG anti-A were detected in the serum. Eluates made from the recipient's RBCs showed the same specificity as serum antibodies. During the third hemolytic episode (Day 160), a mixture of group O and group A RBCs was still present, the direct antiglobulin test was positive (IgG+, C3d-), and anti-Jk(b) and IgG anti-A were observed in the serum and in an eluate made from the patient's RBCs. CONCLUSION: This is the first reported case of severe immune hemolytic anemia due to multiple RBC alloantibodies after an allogeneic bone marrow transplant. The time of appearance and the specificity of the antibodies strongly suggest that they were produced by residual recipient lymphoid cells.     

Blood transfusion costs: a multicenter study

The cost of delivering a unit of blood (whole blood or red cells) to a hospitalized patient was examined in 19 United States teaching hospitals. The average hospital acquisition cost was calculated by using the prices charged by regional blood centers for blood products. To this cost was added an estimate of costs incurred by hospitals for handling, testing, and administering blood. Across study sites, the average hospital cost per unit transfused was $155 and the average charge to the patient was $219. Acquisition cost, the price that hospitals pay for blood, was 37 percent of the total cost to the hospital; the other 63 percent of the hospital cost included costs for blood bank handling (13%), laboratory tests (43%), and blood administration (7%). Significant variations in blood transfusion cost were found within our sample. Most of the variability can be attributed to geographic location of the blood supply source, type of red cell product transfused, prices charged by blood transfusion services, and the frequency of laboratory tests. The results of this transfusion cost study may be helpful in determining the costs of health care delivery, especially when blood transfusions are indicated.     

Predominant role of catalase in the disposal of hydrogen peroxide within human erythrocytes

Purified enzymes were mixed to form a cell-free system that simulated the conditions for removal of hydrogen peroxide within human erythrocytes. Human glutathione peroxidase disposed of hydrogen peroxide (H2O2) at a rate that was only 17% of the rate at which human catalase simultaneously removed hydrogen peroxide. The relative rates observed were in agreement with the relative rates predicted from the kinetic constants of the two enzymes. These results confirm two earlier studies on intact erythrocytes, which refuted the notion that glutathione peroxidase is the primary enzyme for removal of hydrogen peroxide within erythrocytes. The present findings differ from the results with intact cells, however, in showing that glutathione peroxidase accounts for even less than 50% of the removal of hydrogen peroxide. A means is proposed for calculating the relative contribution of glutathione peroxidase and catalase in other cells and species. The present results raise the possibility that the major function of glutathione peroxidase may be the disposal of organic peroxides rather than the removal of hydrogen peroxide.     

Interleukin-4 stimulates human monocytes to produce tissue-type plasminogen activator

Tissue-type plasminogen activator (t-PA) is involved in the lysis of blood clots (fibrinolysis) and is used clinically for this purpose. Endothelial cells are one source of the t-PA present in blood. We report here that interleukin-4 (IL-4) (0.1 to 0.25 U/mL; 1 to 3 x 10(- 11) mol/L), but not interferon-gamma (IFN-gamma), elevates t-PA messenger (m)RNA expression and secretion of t-PA activity by human monocytes, with the maximum response at 2.5 U/mL. Supernatant t-PA activity was detected within three hours of exposure to IL-4 and maximum activity within six hours. Thus, IL-4 may control fibrin deposition at sites of inflammation during cell-mediated immune responses, as well as having a therapeutic role in thrombolysis.     

Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation

Necrotizing enterocolitis is a devastating inflammatory condition of the intestine that occurs almost exclusively in premature newborns. Although its exact pathogenesis is unclear, we have postulated that it may result from a predisposition of the immature intestine to mount an unusually robust and damaging response to microbial infection. In support of this idea, we report that the IL-8 response of an immature human enterocyte cell line to bacterial infection was significantly higher than that of a mature enterocyte cell line. The response in both cell lines was flagellin-dependent. Corresponding to the difference in IL-8 production, the immature enterocytes expressed appreciably lower levels of specific IkappaB genes when compared with the mature enterocytes. Similar developmentally regulated differences in cytokine response and IkappaB expression were also seen in primary rat enterocytes, indicating that these observations were not peculiarities of the cell lines. Furthermore, when the level of IkappaBalpha expression was increased in the immature cell line by transfection, the flagellin-dependent IL-8 response was attenuated. Thus, we have demonstrated a previously undescribed developmental regulation of IkappaB expression in the intestine involved in modulating the IL-8 response to bacterial infection, which may contribute to the pathogenesis of age-specific inflammatory bowel diseases such as necrotizing enterocolitis.