Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis.

The localization of the TCR and other signaling molecules in membrane rafts (MR) is essential for the activation of T lymphocytes. MR are stabilized by sphingolipids and cholesterol. Activation of T lymphocytes leads to the confluence of small MR and the formation of an immunological synapse that is essential for sustained activation and proliferation.

DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function.

The checkpoint kinase Chk1 is an established transducer of ATR- and ATM-dependent signalling in response to DNA damage. In addition to its nuclear localization, Chk1 localizes to interphase centrosomes and thereby negatively regulates entry into mitosis by preventing premature activation of cyclin B-Cdk1 during unperturbed cell cycles. Here, we demonstrate that DNA damage caused by ultraviolet irradiation or hydroxyurea treatment leads to centrosomal accumulation of endogenous Chk1 in normal human BJ fibroblasts and in ATR- or ATM-deficient fibroblasts.

Hemostatic parameters after hepatectomy for cancer.

Background/aims: Epidural analgesia improves postoperative outcome, and should benefit patients undergoing hepatectomy for cancer. However, the combination of underlying disease, surgery, and blood loss after hepatectomy may lead to hemostatic changes that, theoretically, increase the risk of epidural hematoma. To quantify these changes, we retrospectively reviewed the records of 229 patients at the Prince of Wales Hospital, Hong Kong.

Serum cytokeratin-18 fragments as quantitative markers of epithelial apoptosis in liver and intestinal graft-versus-host disease.

Graft-versus-host disease (GVHD) is the main complication of allogeneic stem cell transplantation. However, diagnosis of GVHD and evaluation of response to immunosuppressive treatment is sometimes difficult. Since apoptosis is the histopathologic hallmark in GVHD, we investigated whether active GVHD-induced target organ destruction is mirrored by serum levels of the caspase-cleaved neo-epitope of cytokeratin-18 fragments (CK18Fs).

Effect of an integrated teaching intervention on clinical decision analysis: a randomized, controlled study of undergraduate medical students.

A four-hour integrated teaching session on clinical decision analysis has been developed and introduced as part of the Life Long Learning Skills course for medical students at The Chinese University of Hong Kong. The feasibility and effectiveness of teaching the principles and practice of clinical decision analysis to final-year undergraduate medical students was evaluated. One hundred and thirty-two students were randomly assigned to medical (intervention) and surgical rotations (control) and were assessed two weeks before and three weeks following a teaching session.

Primitive and committed human hematopoietic progenitor cells interact with primary murine neural cells and are induced to undergo self-renewing cell divisions.

Objective: Studies in animal models have indicated that hematopoietic progenitor cells (HPC) migrate and home to the central nervous system and might acquire neural features under specific circumstances. The interaction between HPC and the neural environment and the functional effect on hematopoiesis have not yet been defined.

Methods: CD34(+)133(+) cells from mobilized peripheral blood were cocultured with primary murine neurons or astrocytes.

Flooding with carbon dioxide prevents airway fire induced by diathermy during open tracheostomy.

Background: Open tracheostomy is commonly performed during head and neck surgery, and in critically ill patients. Diathermy-induced airway fire during tracheotomy is rare but may have grave implications. Recommendations to minimize this risk are not always practical.

Low rate of long-lasting remissions after successful treatment of immune thrombocytopenic purpura with rituximab.

Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura, is thought to be caused primarily by the production of autoantibodies directed against platelet surface glycoproteins. Treatment of an acute ITP episode can be difficult, and relapses are common. Recent studies have shown that the anti-CD20 antibody rituximab is effective in the treatment of relapsed and refractory patients.

Identification of griseofulvin as an inhibitor of centrosomal clustering in a phenotype-based screen.

A major drawback of cancer chemotherapy is the lack of tumor-specific targets which would allow for the selective eradication of malignant cells without affecting healthy tissues. In contrast with normal cells, most tumor cells contain multiple centrosomes, associated with the formation of multipolar mitotic spindles and chromosome segregation defects. Many tumor cells regain mitotic stability after clonal selection by the coalescence of multiple centrosomes into two functional spindle poles.

Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors.

Mesenchymal stromal cells (MSC) provide a supportive cellular microenvironment and are able to maintain the self-renewal capacity of hematopoietic progenitor cells (HPC). Isolation procedures for MSC vary extensively, and this may influence their biologic properties. In this study, we have compared human MSC isolated from bone marrow (BM) using two culture conditions, from cord blood (CB), and from adipose tissue (AT).

Atrial-radiofrequency catheter ablation mediated targeting of mesenchymal stromal cells.

Sinus node dysfunction and high-degree heart block are the major causes for electronic pacemaker implantation. Recently, genetically modified mesenchymal stromal cells (MSCs, also known as "mesenchymal stem cells") were demonstrated to generate pacemaker function in vivo. However, experimental approaches typically use open thoracotomy for direct cell injection into the myocardium.

The many facets of SDF-1alpha, CXCR4 agonists and antagonists on hematopoietic progenitor cells.

Stromal cell-derived factor-1alpha (SDF-1alpha) has pleiotropic effects on hematopoietic progenitor cells (HPCs). We have monitored podia formation, migration, proliferation, and cell-cell adhesion of human HPC under the influence of SDF-1alpha, a peptide agonist of CXCR4 (CTCE-0214), a peptide antagonist (CTCE-9908), and a nonpeptide antagonist (AMD3100). Whereas SDF-1alpha induced migration of CD34(+) cells in a dose-dependent manner, CTCE-0214, CTCE-9908, and AMD3100 did not induce chemotaxis in this concentration range albeit the peptides CTCE-0214 and CTCE-9908 increased podia formation.

The beauty of asymmetry: asymmetric divisions and self-renewal in the haematopoietic system.

Purpose Of Review: The hallmark of stem cells is their dual abilities to self-renew and to differentiate into multiple lineages. To fulfill these functions they must undergo asymmetric division. A central question in developmental biology is how can a single cell divide to produce two progeny cells that adopt different fates? We provided evidence of the significance of asymmetric division in human haematopoietic stem cells.

Differences in functional activity and antigen expression of granulocytes primed in vivo with filgrastim, lenograstim, or pegfilgrastim.

Background: Granulocyte-colony-stimulating factor (G-CSF) is known to affect functional activity and antigen expression of neutrophil granulocytes. Beside nonglycosylated filgrastim and glycosylated lenograstim, pegylated filgrastim (pegfilgrastim) has recently been introduced for single administration into clinical use.

Study Design And Methods: Here, granulocytes from 27 patients with nonmyeloid malignancies were compared functionally (migration, reactive oxygen species production, and G-CSF serum levels) and phenotypically (cell surface antigen expression) before and after G-CSF administration.

Cytokine-induced killer cells targeted by the novel bispecific antibody CD19xCD5 (HD37xT5.16) efficiently lyse B-lymphoma cells.

Due to their dual binding capacity, bispecific antibodies (bsAb) can be used to cross-link cytotoxic effector cells with malignant targets and may thereby improve adoptive immunotherapy. In this study, the development and preclinical testing of the quadroma-derived bsAb HD37xT5.16 of the specificity CD19xCD5 is reported.

Functional diagnosis of residual lymphomas after radiochemotherapy with positron emission tomography comparing FDG- and FLT-PET.

Positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) is used as a functional imaging technique for the staging and follow-up of lymphomas. However, additional information about the tumor proliferation rate using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) may be useful for the assessment of prognosis. We enrolled 48 patients with Hodgkin's (n = 15) and non-Hodgkin's lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG and FLT.

Mitogen-activated protein kinase phosphatase-1 (MKP-1) preferentially dephosphorylates p42/44MAPK but not p38MAPK in rat pinealocytes.

We recently reported a diurnal and norepinephrine (NE) -induced expression of mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the rat pineal gland and postulated that this MKP-1 expression might impact adrenergic-regulated arylalkylamine-N-acetyltransferase (AA-NAT) activity via modulation of MAPKs. In this study, we investigated the effect of depletion of MKP-1 expression by using doxorubicin, a topoisomerase inhibitor that suppresses the expression of MKP-1 in other cell types and small interfering RNA targeted against Mkp1 in NE-stimulated pinealocytes. We found that both treatments were effective in inhibiting NE induction of MKP-1 expression.

High rate of centrosome aberrations and correlation with proliferative activity in patients with untreated B-cell chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (CLL) is characterized by a high rate of clonal genomic alterations and a low proliferative activity with cell cycle arrest in G(0)/G(1) phase. Recently, centrosome aberrations have been described as a possible cause of chromosomal instability and aneuploidy in many human malignancies. To investigate whether centrosome aberrations do occur in CLL and whether they correlate with common prognostic factors and disease activity, we examined peripheral blood mononuclear cells (PBMC) from 70 patients with previously untreated CLL using an antibody to gamma-tubulin.

Results of a phase I dose-escalation study using single-fraction stereotactic radiotherapy for lung tumors.

Background: The purpose of this study was to report initial results of a phase I study using single-fraction stereotactic radiotherapy (RT) in patients with inoperable lung tumors.

Methods: Eligible patients included those with inoperable T1-2N0 non-small cell lung cancer (NSCLC) or solitary lung metastases. Treatments were delivered by means of the CyberKnife.

Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells.

Substrate-adherent cultured cells derived from human bone marrow or umbilical cord blood ("mesenchymal stem cells") are of special interest for regenerative medicine. We report that such cells, which can display considerable heterogeneity with respect to their cytoskeletal protein complement, are often interconnected by special tentacle-like cell processes contacting one or several other cells. These processus adhaerentes, studded with many (usually small) puncta adhaerentia and varying greatly in length (up to more than 400 microm long), either contact each other in the intercellular space ("ET touches") or insert in a tight-fitting manner into deep plasma membrane invaginations (recessus adhaerentes), thus forming a novel kind of long (up to 50 microm) continuous cuff-like junction (manubria adhaerentia).

Intravenous delivery of autologous mesenchymal stem cells limits infarct size and improves left ventricular function in the infarcted porcine heart.

Systemic delivery of bone marrow-derived mesenchymal stem cells (MSCs) is a noninvasive approach for myocardial repair. We aimed to test this strategy in a pig model of myocardial infarction. Pigs (n = 8) received autologous MSCs (1 x 10(6)/kg body weight) labeled with fluorescent dye 48 h post proximal left anterior descending artery (LAD) occlusion.