Hemin does not cause commitment of murine erythroleukemia (MEL) cells to terminal differentiation

The effect of hemin on the differentiation program of murine erythroleukemia (MEL) cells has been investigated. While hemin treatment does induce increased levels of globin mRNA and hemoglobin, it fails to lead to other biochemical changes associated with MEL cell differentiation induced by DMSO and thioguanine. These include increased levels of the nuclear protein IP25 and of the enzyme cytidine deaminase. Clonal analysis of hemin-treated cells revealed that unlike other inducers, hemin does not cause a reprogramming of MEL cells to a specific limitation of proliferative capacity. These observations suggest that hemin differs from DMSO and thioguanine in that it exerts specific effects on globin expression in MEL cells without triggering commitment to the terminal differentiation program.     

KRDS--a tetrapeptide derived from lactotransferrin--inhibits binding of monoclonal antibody against glycoprotein IIb-IIIa on ADP-stimulated platelets and megakaryocytes

Short peptides isolated from fibrinogen and K-casein have been shown to inhibit platelet aggregation and fibrinogen binding to stimulated platelets. We studied the effects of synthetic peptides occurring in milk proteins (bovine K-casein, KNQDK, and human lactotransferrin, KRDS) and in fibrinogen (RGDS and L10) on subsequent binding of monoclonal antibodies (MoAb) against the glycoprotein (GP) IIb-IIIa complex (AP2 and P2) on adenosine diphosphate (ADP)-stimulated and unstimulated human platelets and megakaryocytes (MKs) by using an immunoperoxidase method to visualize antibody binding. Only KRDS (900 mumol/L) inhibited the binding of AP2 and P2 on ADP (5 mumol/L)- stimulated platelets, but not on unstimulated platelets. However, the binding of P2 was considerably more inhibited than that of AP2 as judged by immunoperoxidase intensity. Radiolabeled AP2 binding was inhibited by 30% with KRDS on ADP-stimulated platelets as compared with platelets incubated in the absence of ADP. KRDS did not inhibit the binding of MoAbs against GP IIIa (SZ 21), GP IIb (SZ 22), and GP Ib (SZ 2) on ADP-stimulated human platelets. Inhibition of P2 binding by KRDS was also observed in a section of MKs isolated from human bone marrow and stimulated by 15 or 20 micron ADP. A lower concentration of ADP (5 or 10 mumol/L) failed to produce any inhibition of binding. This indicates that MKs may not be equally responsive to agonists as platelets. Moreover, P2 binding inhibition was observed in a larger (P less than .001) percentage of mature MKs (29%) as compared with younger, maturing MKs (11%). The observations suggested that a functional ability possessed by platelets, namely, agonist-induced exposure of the site of interaction of KRDS, may occur at a late stage of MK development.     

Exacerbated experimental arthritis in Wiskott–Aldrich syndrome protein deficiency: Modulatory role of regulatory B cells

Patients deficient in the cytoskeletal regulator Wiskott–Aldrich syndrome protein (WASp) are predisposed to varied autoimmunity, suggesting it has an important controlling role in participating cells. IL‐10‐producing regulatory B (Breg) cells are emerging as important mediators of immunosuppressive activity. In experimental, antigen‐induced arthritis WASp‐deficient (WASp knockout [WAS KO]) mice developed exacerbated disease associated with decreased Breg cells and regulatory T (Treg) cells, but increased Th17 cells in knee‐draining LNs. Arthritic WAS KO mice showed increased serum levels of B‐cell‐activating factor, while their B cells were unresponsive in terms of B‐cell‐activating factor induced survival and IL‐10 production. Adoptive transfer of WT Breg cells ameliorated arthritis in WAS KO recipients and restored a normal balance of Treg and Th17 cells. Mice with B‐cell‐restricted WASp deficiency, however, did not develop exacerbated arthritis, despite exhibiting reduced Breg‐ and Treg‐cell numbers during active disease, and Th17 cells were not increased over equivalent WT levels. These findings support a contributory role for defective Breg cells in the development of WAS‐related autoimmunity, but demonstrate that functional competence in other regulatory populations can be compensatory. A properly regulated cytoskeleton is therefore important for normal Breg‐cell activity and complementation of defects in this lineage is likely to have important therapeutic benefits.     

Cytogenetic events after bone marrow transplantation for chronic myeloid leukemia in chronic phase

Forty-eight patients treated by allogeneic bone marrow transplantation (BMT) for Philadelphia (Ph) chromosome-positive chronic myeloid leukemia in chronic phase had serial cytogenetic studies of marrow performed at intervals after transplant. Twenty patients received marrow cells from donors of opposite sex. Ph+ marrow metaphases were identified in 24 of 48 (50%) of patients after BMT; they were first seen early (within 1 year) in 16 cases and late (greater than 1 year after BMT) in eight cases. Ph-positivity after BMT occurred more commonly in recipients of T-depleted than nondepleted marrow (19 of 28 v 5 of 20). In 4 cases the Ph+ metaphases were found only transiently after BMT; in 11 cases the Ph+ metaphases have persisted but hematologic relapse has not ensued; in 9 cases the finding of Ph+ metaphases coincided with or preceded hematologic relapse. Chromosomes in cells of donor origin had morphological abnormalities in two cases. No relapses were identified in cells of donor origin. Our data suggest that the relationship between cells of recipient and donor origin is complex: cure of leukemia may depend on factors that operate for some months or years after BMT.     

Computed tomography-guided percutaneous core needle biopsy in pancreatic tumor diagnosis

AIM: To evaluate the techniques, results, and complications related to computed tomography(CT)-guided percutaneous core needle biopsies of solid pancreatic lesions.METHODS: CT-guided percutaneous biopsies of solid pancreatic lesions performed at a cancer reference center between January 2012 and September 2013 were retrospectively analyzed. Biopsy material was collected with a 16-20 G Tru-Core needle(10-15 cm; Angiotech, Vancouver, CA) using a coaxial system and automatic biopsy gun. When direct access to the lesion was not possible, indirect(transgastric or transhepatic) access or hydrodissection and/or pneumodissection maneuvers were used. Characteristics of the patients, lesions, procedures, and histologic results were recorded using a standardized form. RESULTS: A total of 103 procedures included in the study were performed on patients with a mean age of 64.8 year(range: 39-94 year). The mean size of the pancreatic lesions was 45.5 mm(range: 15-195 mm). Most(75/103, 72.8%) procedures were performed via direct access, though hydrodissection and/or pneumodissection were used in 22.2%(23/103) of cases and indirect transhepatic or transgastric access was used in 4.8%(5/103) of cases. Histologic analysis was performed on all biopsies, and diagnoses were conclusive in 98.1%(101/103) of cases, confirming3.9%(4/103) of tumors were benign and 94.2%(97/103) were malignant; results were atypical in 1.9%(2/103) of cases, requiring a repeat biopsy to diagnose a neuroendocrine tumor, and surgical resection to confirm a primary adenocarcinoma. Only mild/moderate complications were observed in 9/103 patients(8.7%),and they were more commonly associated with biopsies of lesions located in the head/uncinate process(n =8), than of those located in the body/tail(n = 1) of the pancreas, but this difference was not significant.CONCLUSION: CT-guided biopsy of a pancreatic lesion is a safe procedure with a high success rate, and is an excellent option for minimally invasive diagnosis.     

Discrimination in Healthcare Settings is Associated with Disability in Older Adults: Health and Retirement Study, 2008–2012

BACKGROUND

As our society ages, improving medical care for an older population will be crucial. Discrimination in healthcare may contribute to substandard experiences with the healthcare system, increasing the burden of poor health in older adults. Few studies have focused on the presence of healthcare discrimination and its effects on older adults.

OBJECTIVE

We aimed to examine the relationship between healthcare discrimination and new or worsened disability.

DESIGN

This was a longitudinal analysis of data from the nationally representative Health and Retirement Study administered in 2008 with follow-up through 2012.

PARTICIPANTS

Six thousand and seventeen adults over the age of 50 years (mean age 67 years, 56.3 % female, 83.1 % white) were included in this study.

MAIN MEASURES

Healthcare discrimination assessed by a 2008 report of receiving poorer service or treatment than other people by doctors or hospitals (never, less than a year=infrequent; more than once a year=frequent). Outcome was self-report of new or worsened disability by 2012 (difficulty or dependence in any of six activities of daily living). We used a Cox proportional hazards model adjusting for age, race/ethnicity, gender, net worth, education, depression, high blood pressure, diabetes, cancer, lung disease, heart disease, stroke, and healthcare utilization in the past 2 years.

KEY RESULTS

In all, 12.6 % experienced discrimination infrequently and 5.9 % frequently. Almost one-third of participants (29 %) reporting frequent healthcare discrimination developed new or worsened disability over 4 years, compared to 16.8 % of those who infrequently and 14.7 % of those who never experienced healthcare discrimination (p < 0.001). In multivariate analyses, compared to no discrimination, frequent healthcare discrimination was associated with new or worsened disability over 4 years (aHR = 1.63, 95 % CI 1.16–2.27).

CONCLUSIONS

One out of five adults over the age of 50 years experiences discrimination in healthcare settings. One in 17 experience frequent healthcare discrimination, and this is associated with new or worsened disability by 4 years. Future research should focus on the mechanisms by which healthcare discrimination influences disability in older adults to promote better health outcomes for an aging population.

Electronic supplementary material

The online version of this article (doi:10.1007/s11606-015-3233-6) contains supplementary material, which is available to authorized users.KEY WORDS: disability, discrimination, geriatrics     

羟基磷灰石骨水泥中碳酸根存在的意义及其与组织的相容性

目的:观察碳酸化羟基磷灰石骨水泥与磷酸钙骨水泥的组织学反应差异,判定羟基磷灰石骨水泥中碳酸根存在的意义及其对组织相容性的影响。方法:实验于2000-01/2002-08在解放军总医院骨科研究所及医学动物实验中心完成。①碳酸化羟基磷灰石骨水泥的制备:以碳酸钙、磷酸三钙、磷酸氢钙等化学试剂为原材料,合成碳酸化羟基磷灰石骨水泥粉体。以磷酸氢二钠和磷酸二氢钠合成0.2mol/L磷酸钠缓冲液,作为固化液。固相/液相=1g/0.4mL。②细胞毒性实验:以磷酸钙骨水泥为对照,观察碳酸化羟基磷灰石骨水泥与骨髓基质细胞共培养后细胞的形态以及与材料表面的黏附性,并分别于2,4,6,8d用MTT法测量细胞的相对增殖率。③肌内埋植实验:选用成年新西兰兔8只,按随机数字表法分为实验组和对照组,每组4只。实验组将碳酸化羟基磷灰石预制成形,植入家兔背部肌肉组织内。对照组动物植入磷酸钙骨水泥。术后2,4,8,12周每组分别麻醉处死1只,观察材料周围组织的炎性反应和纤维包膜的形成情况。结果:纳入动物8只,均进入结果分析。①碳酸化羟基磷灰石骨水泥和磷酸钙骨水泥的浸提液分别与兔骨髓基质细胞共培养后,细胞的形态、与材料表面的黏附性以及细胞相对增殖率等无显著差别。②两种材料植入家兔背部肌肉内,材料周围形成的纤维组织包膜厚度均低于30μm,均未发现炎性细胞反应。植入12周时实验组碳酸化羟基磷灰石骨水泥的平均包膜厚度略低于对照组磷酸钙骨水泥(分别为22.7,26.1μm)。结论:碳酸化羟基磷灰石骨水泥和磷酸钙骨水泥均具有优秀的组织相容性,碳酸根的存在可以减少羟基磷灰石骨水泥的组织反应。