Can Boga

Human bone marrow mesenchymal cells express NG2: possible increase in discriminative ability of flow cytometry during mesenchymal stromal cell identification

BACKGROUND AIMS Mesenchymal stromal cells (MSC) exhibit non-specific hematopoietic cell and/or stromal cell markers (e.g. CD73, CD105 and CD166) that have been used to identify MSC by flow cytometry. Because a neural glial antigen, NG2 (a progenitor cell marker in the central nervous system), is expressed by several tissue cells originating in the mesenchyme but not hematopoietic cells, it might be useful for isolating and identifying MSC. We investigated NG2 expression on culture-expanded MSC by flow cytometry. METHODS Human bone marrow (BM) samples taken from 12 donors were cultured for MSC to be used in up to nine serial passages. Using flow cytometry, the neural glial antigen NG2 and commonly used MSC markers CD73, CD105 and CD166, were analyzed on the surface of culture-expanded MSC. The multipotential differentiation of the MSC was examined by adipogenic and osteogenic induction. RESULTS The percentage of cells positive for NG2 was similar to the percentages of cells positive for CD73, CD105 and CD166 in all passages of BM samples. The mean fluorescent intensities of NG2 did not change with culture passage. The MSC was successfully differentiated into adipogenic and osteogenic lines. The cells showed no karyotypic abnormalities. CONCLUSIONS NG2 seems to be a promising marker for investigating the biology of MSC.

Conventional and molecular cytogenetic findings of myelodysplastic syndrome patients.

AbstractMyelodysplastic syndrome (MDS) involves myeloid cells of the bone marrow, which is important in progressive bone marrow insufficiency. Of all MDS patients, 40%–50% have at least one chromosomal rearrangement. Loss of specific chromosomal regions like 5q– and 7q– are usually the secondary cytogenetic abnormalities associated with MDS. In order to detect chromosome abnormalities associated with MDS, bone marrow samples from 26 patients diagnosed as MDS were obtained prior to chemotherapy. Both conventional cytogenetic analyses and fluorescence in situ hybridisation (FISH) methods were performed and locus–specific probes for 5q and 7q were used. Results obtained were compared. Twenty–one patients had normal karyotypes and four patients had abnormal karyotypes, while in one patient we could not obtain metaphases from cultures. Three patients with normal karyotypes revealed del (5q), two patients had del (7q) and one patient had monosomy (7). A total of 10 of 26 patients had chromosome changes visualised by either conventional or molecular cytogenetics (~38.5%). Our results show that both methods are important in diagnosis and follow up of MDS patients. When used together, conventional cytogenetics and FISH detect clinically significant chromosome abnormalities in MDS patients.

Prophylactic red blood cell exchange may be beneficial in the management of sickle cell disease in pregnancy

Sickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX).

Pregnancy and sickle cell disease: A review of the current literature.

Sickle cell disease (SCD) is the most common hereditary disease worldwide, presenting with anemia and intermittent severe pain. Pregnancy in a patient with SCD is associated with high levels of maternal and fetal morbidity and mortality; the maternal and fetal death rates during pregnancy can attain 11.4% and 20%, respectively. Patient care has improved over time. However, certain management issues remain unresolved; these include the optimum policy in terms of prophylactic blood transfusion, and the use of antiplatelet drugs. Such issues are attributable to the heterogeneous nature of clinical SCD features, and the limitations of uncontrolled and prospective trials. In this review, we seek to facilitate a better understanding of relevant issues via creation of a comparative data profile extracted from current studies. This report may also encourage the drafting of standard operating procedure for management of pregnancy in SCD patients.

Long-term colchicine therapy in a patient with Behçet's disease and acute promyelocytic leukemia

Behçet’s disease causes a continuous T-lymphocytic mediated inflammatory reaction in the small arterioles, which results in gradual destruction of any human organ or system. The benefit of treatment with colchicine in patients with Behçet’s disease has been reported in literature. Acute leukemia has seldom been associated with Behçet’s disease, although acute promyelocytic leukemia is a particular subtype of leukemia that is often characterized by special cytogenetic abnormalities. We report a male patient with acute promyelocytic leukemia and Behçet’s disease who had received long-term treatment with colchicine. To our knowledge, this is the first report of the concomitant occurrence of acute promyelocytic leukemia and Behçet’s disease, which suggests that long-term colchicine therapy has a role in the pathogenesis of acute promyelocytic leukemia. The patient described has been treated with retinoic acid and idarubicin (the ATRA-IDA protocol). At the time of this writing, his disease is in clinical remission.

Therapeutic Potential of Apigenin, a Plant Flavonoid, for Imatinib-Sensitive and Resistant Chronic Myeloid Leukemia Cells

Despite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenins effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and gene networks that are modulated in CML in response to apigenin. Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.

Safety, therapeutic effectiveness, and cost of parenteral iron therapy

Patients have to discontinue the use of oral iron therapy due to the development of side effects and lack of long-term adherence to medication for iron deficiency anemia. This study aimed to evaluate the therapeutic effectiveness, safety, and cost of intravenous iron sucrose therapy. The computerized database and medical records of 453 patients diagnosed with iron deficiency anemia who received intravenous iron sucrose therapy for iron deficiency anemia between 2004 and 2008 were reviewed. The improvement of hematologic parameters and cost of therapy were evaluated 4 weeks after therapy. 453 patients (443 females, 10 males; age: 44.2 ± 12.3 years) received iron sucrose therapy. Mean hemoglobin, hematocrit, and mean corpuscular volume values were 8.2 ± 1.4 g/dL, 26.9 ± 3.8%, and 66.1 ± 7.8 fL, respectively, before therapy and 11.5 ± 1.0 g/dL, 35.8 ± 2.5%, 76.5 ± 6.1 fL, respectively, after therapy (P < 0.001). A mean ferritin level of 3.4 ± 2.4 ng/mL before therapy increased to 65.9 ± 40.6 ng/mL after therapy (P < 0.001). All patients responded to intravenous iron therapy (transferrin saturation values of the patients were >50%). The mean cost of therapy was 143.07 ± 29.13 US dollars. The therapy was well tolerated. Although the cost of intravenous iron sucrose therapy may seem high, a lack of adherence to therapy and side effects including gastrointestinal irritation during oral iron therapy were not experienced during intravenous therapy.

The association of pagophagia with Helicobacter pylori infection in patients with iron-deficiency anemia

This study aimed to determine the relationship between pagophagia (compulsive ice eating) and H.pylori infection in patients with iron-deficiency anemia. We identified H.pylori infection using the 13C-urea breath test in 45 patients with iron-deficiency anemia (group 1) and 55 patients with iron-deficiency anemia and pagophagia (group 2). Subgroups for testing oral intestinal iron absorption were randomly assigned from both groups. These subgroups consisted of (a) 10 patients with iron-deficiency anemia, (b) 10 patients with iron-deficiency anemia and pagophagia, (c) 10 patients with iron-deficiency anemia, pagophagia, and H.pylori infection before the eradication of H.pylori and (d) subgroup c after eradication therapy. There was no difference in the rate of H.pylori infection in the iron-deficiency anemia groups, with or without pagophagia. Furthermore, oral intestinal iron absorption was not influenced by pagophagia and/or H.pylori infection. Pagophagia did not increase the risk of H.pylori infection in patients with iron-deficiency anemia. Pagophagia and H.pylori infection do not synergistically affect the development of intestinal iron absorption abnormalities.

The apoptosis of blood polymorphonuclear leukocytes in sickle cell disease

The apoptosis of human polymorphonuclear leukocytes (PMNs) in patients with sickle cell disease (SCD) is not well understood. The goal of this study was to examine the apoptosis of PMNs in patients with SCD and in controls.

Bone marrow necrosis: a rare complication of herbal treatment with Hypericum perforatum (St. John's wort).

A 22-year-old man presented with fever and ulceration of the oral mucosa. The patient had pharyngeal and esophageal candidiasis. For the 3 weeks prior to presentation, he had been taking approximately 1000 mg/day of flowering herbs (Hypericum perforatum L, known as St. Johns wort) for treatment of depression. A complete blood count on the first day of hospitalization showed agranulocytosis and normocytic anemia. His condition worsened, and he developed progressive dysphagia. A bone marrow biopsy on day 3 revealed bone marrow necrosis. After the diagnosis was established (day 3 of hospitalization), treatment with granulocyte colony-stimulating factor 48 U/day, intravenous immunoglobulin 400 mg/kg, and amphotericin B 100 mg/day was initiated. The patient did not respond, and died within one week of the diagnosis. This cases suggests that Hypericum species may lead to severe hematologic toxicity, with conditions involving bone marrow necrosis.