Lineage promiscuity in hemopoietic differentiation and leukemia

An increasing number of reports document instances in which individual leukemic cells coexpress markers normally believed to be restricted to a single lineage. This has been interpreted by McCulloch and colleagues as aberrant programming or lineage infidelity and contrasts with earlier suggestions that lineage fidelity of gene expression was usually maintained in leukemia. We argue that several examples of infidelity are suspect on technical grounds, whereas others are bona fide and require explanation, eg, partial rearrangements and expression of Ig heavy-chain and/or T cell receptor genes in inappropriate cells and terminal deoxynucleotidyl transferase in leukemic myeloblasts. Individual examples of truly aberrant gene expression may well occur in leukemia but with insufficient regularity to be of general significance. We suggest that verifiable and consistent examples of apparent lineage infidelity do not reflect genetic misprogramming but rather the existence of a transient phase of limited promiscuity of gene expression occurring in normal biopotential or multipotential progenitors and able to be preserved as a relic in leukemic blast cell populations that are in maturation arrest. This alternative explanation has interesting implications for mechanisms of hematopoietic differentiation and leads to some testable predictions.     

Does diabetes increase cell death in the heart?

Indian Journal of Thoracic and Cardiovascular Surgery -     

The influence of a hydrogen peroxide and glycerol containing mouthrinse on plaque accumulation: a 3-day non-brushing model

Abstract: Aim: To evaluate the inhibition of plaque growth by an experimental mouthrinse (BioXyl^®) based on hydrogen peroxide/glycerol. Design: It was a double‐blind, randomized study involving 40 volunteers in good general health. At the start of the trial, all participants received a dental prophylaxis to remove all plaque deposits. During the next 3 days subjects refrained from any mechanical oral hygiene procedure, except for the allocated mouthrinse being either the hydrogen peroxide (H₂O₂; 0.013% H₂O₂/0.004% glycerol) or the placebo without H₂O₂. At the third day of appointment, plaque levels were assessed at six sites per tooth. Results: The test group had a mean overall plaque score of 2.66 and the placebo group of 2.70. The difference in plaque scores between the two groups was not statistically significant. Conclusions: The results of this pilot study showed that there was no statistically significant difference between the H₂O₂/glycerol group and the placebo group with respect to plaque inhibition within this study design.     

胃粘膜上皮异型增生--帕多瓦国际分类

病理医生对胃癌癌前病变特别感兴趣,西方国家和日本已提出用不同名称来确定这种病变。因此重要的是取得国际共识,以便在不同研究机构之间,特别在日本和西方研究者之间进行比较。文中提出的这一分类是由不同国家的病理学专家专门提出的,下列序号为原分类编号。1　无异型增生1.0　正常　粘膜成分即胃小凹、腺颈部、腺体和间质完好地保持其位置和比例,炎细胞浸润轻微或缺乏。1.1　反应性胃小凹上皮增生　见于胃粘膜对有丝分裂刺激物反应时,可能是感染性的,也可能是化学性的,或是在糜烂、溃疡后的增生。胃小凹延长、弯曲;细胞核增大,有时染色质…     

Vertebroplasty in the management of traumatic burst fractures: A case series

This study aimed to assess the role of percutaneous vertebroplasty (VP) in the management of acute traumatic burst fractures. We describe three cases where percutaneous VP was carried out for traumatic non‐osteoporotic burst vertebral fractures. For clinical symptoms and the effect of the VP procedure to be assessed, all patients completed a visual analogue scale and a mobility score before the procedure and at day 1 and 3 months post procedure. Improvements in both pain and mobility scores immediately post procedure were seen in all patients, and these results persisted at 3‐month follow up. Percutaneous VP provided a successful, minimally invasive treatment of these patients' traumatic fractures while avoiding major surgical procedures and associated surgical morbidity and complications.     

Selection of platelets for refractory patients by HLA matching and prospective crossmatching

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.     

Partial chimerism after T-cell-depleted allogeneic bone marrow transplantation in leukemic HLA-matched patients: a cytogenetic documentation

We evaluated serially by cytogenetics the blood and marrow chimerism of 38 leukemic recipients of HLA-matched bone marrow transplants (BMT) who were prepared by high doses of alkylating agents and fractionated total- body irradiation (2.2 Gy X 5). Donor or host mitoses were identified by examination of sex chromosomes in 32 patients or by evaluation of the polymorphism of other chromosomes after specific banding in six patients. Twenty-four patients were recipients of untreated BMT, and 14 were recipients of T-cell-depleted BMT. In the 24 patients who received untreated BMT, all showed successful engraftment, and only three had a transient mixed chimera. In the 14 recipients of T-cell-depleted BMTs, four rejected their grafts, and seven had mixed chimeras; these mixed chimeras were more frequent in blood lymphocytes than in marrow cells and could be detected up to 26 months after BMT. This high frequency of partial chimerism after T-cell-depleted BMT by comparison with a control group suggests that the donor's T cells play an important role in the eradication of host residual hematopoiesis after allogeneic BMT.     

Cytokines in inflammatory malignant fibrous histiocytoma presenting with leukemoid reaction

Inflammatory malignant fibrous histiocytomas (IMFH) are rare tumors and are frequently associated with leukocytosis. In rare cases, leukemoid reactions were attributed to tumor production of unidentified hematopoietic factors. In this study, we used immunohistochemical techniques to show cytokine immunoreactivity in the malignant cells of two cases of IMFH presenting with leukemoid reactions and compared them with two malignant fibrous histocytomas, noninflammatory type. All four tumors stained positively for stem cell factor (SCF), granulocyte colony-stimulating factor (G-CSF), interleukin-2 (IL-2), IL-4, IL-5, interferon-alpha (IFN-alpha), and insulin-like growth factor-I. Other cytokines detected only in the two IMFH included IL-6, IL-7, IL-8, IFN- gamma, and keratinocyte growth factor. Granulocyte-macrophage-CSF, IL- 3, and transforming growth factor-beta staining was present in one of the two IMFH tumors and was not present in the noninflammatory tumors. The immunohistochemical staining was localized to the malignant cells, suggesting deregulated cytokine expression consistent with their monocytic/histocytic origin. Expression of certain cytokines in the IMFH may account for the local inflammatory infiltrate, tumor fibrosis, and the aggressive nature of the malignant cells. We also detected elevated serum levels of SCF, G-CSF, IL-6, and tumor necrosis factor in one or both of the IMFH patients. These latter observations may explain the bone marrow hypercellularity and other paraneoplastic symptoms, including fever, malaise, and weight loss, observed in both patients. Different cytokines present in the two IMFH tumors appear to be responsible for the eosinophilic leukemoid reaction observed in one case and for the granulocytic leukemoid reaction observed in the other patient. They may also be responsible for expansion of the tumor-cell population, fibroblast proliferation, and enhanced secretion of extracellular collagen.