Acute myeloid leukemia M4 with bone marrow eosinophilia (M4Eo) and inv(16)(p13q22) exhibits a specific immunophenotype with CD2 expression

Extensive immunologic marker analysis was performed to characterize the various leukemic cell populations in eight patients with inv(16)(p13q22) in association with acute myeloid leukemia with abnormal bone marrow eosinophilia (AML-M4Eo). The eight AML cases consisted of heterogeneous cell populations; mainly due to the presence of multiple subpopulations, which varied in size between the patients. However, the immunophenotype of these subpopulations was comparable, independent of their relative sizes. Virtually all AML-M4Eo cells were positive for the pan-myeloid marker CD13. In addition, the AML were partly positive for CD2, CD11b, CD11c, CD14, CD33, CD34, CD36, CDw65, terminal deoxynucleotidyl transferase (TdT), and HLA-DR. Double immunofluorescence stainings demonstrated coexpression of the CD2 antigen and myeloid markers and allowed the recognition of multiple AML subpopulations. The CD2 antigen was expressed by immature AML cells (CD34+, CD14-) and more mature monocytic AML cells (CD34-, CD14+), whereas TdT expression was exclusively found in the CD34+, CD14- cell population. The eight AML-M4Eo cases not only expressed the CD2 antigen, but also its ligand CD58 (leukocyte function antigen-3). Culturing of AML-M4Eo cell samples showed a high spontaneous proliferation in all three patients tested. Addition of a mixture of CD2 antibodies against the T11.1, T11.2, and T11.3 epitopes diminished cell proliferation in two patients with high CD2 expression, but no inhibitory effects were found in the third patient with low frequency and low density of CD2 expression. These results suggest that high expression of the CD2 molecule in AML-M4Eo stimulates proliferation of the leukemic cells, which might explain the high white blood cell count often found in this type of AML.     

RNA干预法特异性抑制核激活因子受体配体诱导破骨细胞的形成

目的:使用RNA干预来特异性减少核激活因子受体配体的表达从而抑制破骨细胞的形成。方法:实验于2005-01/2006-10在解放军第四军医大学全军骨科研究所完成。①构建由U6启动子引导产生小干预RNA的质粒载体mU6pro-dsRANKL。②按0.5,1.0,1.5,2.0,2.5,3.0μg的梯度将质粒mU6pro-dsRANKL及对照质粒mU6pro转染大鼠骨髓基质细胞,48h后提取细胞总RNA。③采用Northern blot法检测,以核激活因子受体配体与内参β-肌动蛋白扩增产物的吸光度比值来反映核激活因子受体配体mRNA的表达情况。④再将质粒mU6pro-dsRANKL按0,1.0,2,3μg转染破骨细胞,抗酒石酸染色显微镜下观察。结果:①Northern blot结果:显示转染骨髓基质细胞后细胞中核激活因子受体配体mRNA的表达量随着质粒载体量的增加而减少。②破骨细胞抗酒石酸染色显示:破骨细胞的数量也随着质粒载体量的增加而减少。结论:U6启动子引导产生小干预RNA的质粒载体能有效的减低核激活因子受体配体的表达从而抑制破骨细胞的形成。     

MARKEDLY ELEVATED ERYTHROCYTE SEDIMENTATION RATES: CONSIDERATION OF CLINICAL IMPLICATIONS IN A HOSPITAL POPULATION

SUMMARY In order to evaluate the clinical significance of very high erythrocyte sedimentation rates (ESRs) we studied 100 consecutive men in a VA Medical Center whose Westergren ESR was more than 100mm/hr. All were followed for up to six months and the ESR-requesting physicians were interviewed. A total of 162 diagnoses known to be associated with an elevated ESR were present in the 90 patients available for follow up. As in most previous series on very high ESRs, infections (seen in 43 patients) were the most common diagnoses. Other diagnoses included: malignancy (16), rheumatologic disease (30), other inflammatory diseases (seven), renal disease (25), and miscellaneous problems (38). Evaluation of 16 patients led to a diagnosis that had not initially been apparent — the ESR-requesting physician did not consider that a high ESR was instrumental in guiding him towards any of these delayed diagnoses. Most of the markedly elevated ESRs in this patient population, requested in the context of already evident serious multisystem disease, contributed little diagnostic information.     

T lymphocytes specific for immunoglobulin allotype. I. Igh- 1(b)-specific T cells demonstrated by suppression in vivo and cytotoxicity in vitro

We show that determinants of IgG(2a) of C57BL/6 mice (Igh-1(b)) stimulate allotypespecific T cells in BALB/c mice. Such cells are detected in two different functional assays; chronic allotype suppression and T cell-mediated cytotoxicity. A population of suppressor T cells capable of inducing chronic Igh-1(b) suppression was demonstrated by rosetting procedures to possess Igh-1(b)-specific receptors, a result interpreted as indicating that suppressor T cells may act directly upon allotype-bearing B cells. From similar populations we were also able to demonstrate Igh-1(b)-specific cytotoxic T cells. Such cells were lytic for target myeloma cells expressing the Igh-1(b) allotype of IgG28, and were ineffective against a variant cell line failing to express Igh-1(b), and other target cell lines expressing different allotypes or isotypes. The similar specificity of suppressor T cells and cytotoxic T lymphocytes for Igh-1(b) allotype raises the possibility that the target in allotype suppression is a B cell, and that allotype-specific cytotoxic T cells may play some role in regulation of allotype expression in the suppressed state.     

Antigen-matched donor blood in the transfusion management of patients with sickle cell disease

BACKGROUND: Alloimmunization to red cell antigens is a significant risk in chronically transfused patients with sickle cell disease. Antigen matching, by decreasing the likelihood of alloantibody development, may significantly facilitate long-term management while decreasing morbidity. STUDY DESIGN AND METHODS: The transfusion records of 86 patients who underwent chronic transfusion for sickle cell disease at a tertiary-care medical center were reviewed retrospectively to determine the efficacy of an antigen-matching program in the prevention of alloimmunization to clinically significant red cell antigens. Recipients were phenotyped and given units matched for the K, C, E, S, and Fya or Fyb antigens. RESULTS: None (0%) of the 40 patients who received antigen-matched transfusions showed any evidence of alloimmunization, while 16 (34.8%) of the 46 patients who received both antigen-matched and non-antigen-matched transfusions developed clinically significant alloantibodies. The cost was 1.8 to 1.5 times that for a standard transfusion protocol. CONCLUSION: On the basis of this experience, it is recommended that transfusion centers engaged in the management of chronically transfused sickle cell anemia patients consider providing antigen-matched units for such patients. This is recommended not only because it prevents alloimmunization but also because such a program provides additional clinical benefits to the patient that may outweigh the higher costs of the process.     

Regulation of the neutralizing anti-hepatitis B surface (HBs) antibody response in vitro in HBs vaccine recipients and patients with acute or chronic hepatitis B virus (HBV) infection

Antibodies directed to the HBs antigen indicate viral clearance and the development of life-long immunity in patients that recovered from HBV infection. In HBs antigen vaccine recipients anti-HBs antibodies provide protective immunity. However, little is known about the regulation of this HBs-specific antibody response. The existence of anti-HBs-secreting B cells was demonstrated using the highly sensitive ELISPOT technique compared with conventional ELISA in serum and cell culture supernatants. In the peripheral blood of patients with acute self-limited hepatitis B, HBs-specific B cells were demonstrated with a high frequency despite undetectable anti-HBs serum antibodies. HBV-immunized patients that had recovered from infection and vaccine recipients had significantly lower frequencies, whereas chronic HBV carriers and negative controls showed no anti-HBs-secreting B cells. Coculture experiments of isolated B and T cells revealed that the anti-HBs antibody response was restricted to the presence of T helper cells, but not to identical HLA class II molecules. Allogeneic T cells derived from vaccine recipients or chronic HBV carriers stimulated the HBs-specific B cell response in HBs vaccine recipients. Otherwise, isolated T helper cells could never provide sufficient help to induce the HBs-specific B cell response in chronic HBV carriers. Furthermore, peripheral blood mononuclear cells (PBMC) of six out of 10 vaccine recipients, one out of five HBV-immunized patients, but of no chronic HBV carrier showed a proliferative response to different HBs antigen preparations. This study demonstrated a high frequency of circulating anti-HBs-producing B cells in the early phase of acute HBV infection, but a lower frequency of HBs-specific B cells years after resolution of HBV infection. In chronic HBV carriers, however, deficient HBs-specific T and B cell responses were observed.     

Complications associated with the use of Port‐a‐Caths in patients with malignant or haematological disease: a single‐centre prospective analysis

HEIBL C., TROMMET V., BURGSTALLER S., MAYRBAEURL B., BALDINGER C., KOPLMÜLLER R., KÜHR T., WIMMER L. & THALER J. (2010) European Journal of Cancer Care 19 , 676–681 Complications associated with the use of Port‐a‐Caths in patients with malignant or haematological disease: a single‐centre prospective analysis Totally implantable central venous catheters are widely used in the management of patients with haematological or malignant disease. This paper investigates device‐related complications and compares it with the literature. A total of 143 Port‐a‐Caths (PaCs) were implanted in 140 patients at a single centre during 2004 and followed until March 2005. Indication for implantation was mainly administration of chemotherapy. High standards of care were applied through intensive training of staff. Complications were registered prospectively and cross‐checked with the medical records at the end of the observational period. The ports were in place for a total of 29 107 days (mean 204, range 3–443 days per port). A total of 25 complications were recorded. These included 13 infections [9.1% with 5 cutaneous (3.5%) and 8 systemic (5.6%) infections], one deep vein thrombosis (0.7%). In 6 patients (4.2%) the device had to be removed because of complications. No device‐related death was observed. The use of totally implantable central venous catheters for treating haemoto‐oncological patients is safe. The need for device removal due to complications was particularly low in this analysis as compared with the literature.     

Effects of an integrated Yoga Program on Self-reported Depression Scores in Breast Cancer Patients Undergoing Conventional Treatment: A Randomized Controlled Trial

Aim:

To compare the effects of yoga program with supportive therapy on self-reported symptoms of depression in breast cancer patients undergoing conventional treatment.

Patients and Methods:

Ninety-eight breast cancer patients with stage II and III disease from a cancer center were randomly assigned to receive yoga (n = 45) and supportive therapy (n = 53) over a 24-week period during which they underwent surgery followed by adjuvant radiotherapy (RT) or chemotherapy (CT) or both. The study stoppage criteria was progressive disease rendering the patient bedridden or any physical musculoskeletal injury resulting from intervention or less than 60% attendance to yoga intervention. Subjects underwent yoga intervention for 60 min daily with control group undergoing supportive therapy during their hospital visits. Beck''s Depression Inventory (BDI) and symptom checklist were assessed at baseline, after surgery, before, during, and after RT and six cycles of CT. We used analysis of covariance (intent-to-treat) to study the effects of intervention on depression scores and Pearson correlation analyses to evaluate the bivariate relationships.

Results:

A total of 69 participants contributed data to the current analysis (yoga, n = 33, and controls, n = 36). There was 29% attrition in this study. The results suggest an overall decrease in self-reported depression with time in both the groups. There was a significant decrease in depression scores in the yoga group as compared to controls following surgery, RT, and CT (P < 0.01). There was a positive correlation (P < 0.001) between depression scores with symptom severity and distress during surgery, RT, and CT.

Conclusion:

The results suggest possible antidepressant effects with yoga intervention in breast cancer patients undergoing conventional treatment.