Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals.

Objective:: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images.

Methods:: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein.

A phase I study of decitabine and rapamycin in relapsed/refractory AML.

A phase I study utilizing decitabine (DAC) followed by the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, in patients with relapsed/refractory adult AML was undertaken to assess safety and feasibility. Patients received DAC 20mg/m(2) intravenously daily for 5 days followed by rapamycin from day 6 to day 25 at doses of 2 mg, 4 mg, and 6 mg/day in a standard 3+3 dose escalation design. Twelve patients completed treatment for safety evaluation.

Botulinum toxin B in the treatment of craniofacial hyperhidrosis.

Background: Hyperhidrosis affects up to 3% of the population and negatively affects patients' quality of life. Craniofacial hyperhidrosis is a common complaint which has been successfully treated with botulinum toxin B (Btx B) since 2004 at our hidrosis clinics.

Objective: To evaluate the safety and clinical effect of Btx B in craniofacial hyperhidrosis.

Botulinum toxin type A and B improve quality of life in patients with axillary and palmar hyperhidrosis.

Hyperhidrosis is a common disorder that may have a severe impact on quality of life. The aim of this study was to investigate the clinical effect of two novel botulinum toxins, Xeomin®, a type A botulinum toxin, and Neuro-bloc®, a type B botulinum toxin, in the treatment of axillary and palmar hyperhidrosis. A total of 84 patients, 58 with axillary and 26 with palmar hyperhidrosis, were included in this open study.

Proteasome inhibition in myelodysplastic syndromes and acute myelogenous leukemia cell lines.

In this work, effects of bortezomib on apoptosis, clonal progenitor growth, cytokine production, and NF-κB expression in patients with MDS with cytopenias requiring transfusion support are examined. Bortezomib increased apoptosis in marrow mononuclear cells but had no effects on CFU-GM, BFU-E, or CFU-L content. No consistent effects on NF-κB activation in vivo were noted.

Cytotoxicity of algae extracts on normal and malignant cells.

Algae preparations are commonly used in alternative medicine. We examined the effects of algae extracts on normal hematopoietic cells and leukemia cells. Ethanol extracts were prepared of Dunaliella salina (Dun), Astaxanthin (Ast), Spirulina platensis (Spir), and Aphanizomenon flos-aquae (AFA).

Influence of marine reserves on coral disease prevalence.

Predicted increases in disease with climate warming highlight the need for effective management strategies to mitigate disease effects in coral communities. We examined the role of marine protected areas (MPAs) in reducing disease in corals and the hypothesis that the composition of fish communities can influence coral health, by comparing disease prevalence between MPA and non-protected (control) reefs in Palau. Overall, the prevalence of diseases pooled, as well as the prevalence of skeletal eroding band (SEB), brown band disease (BrB) and growth anomalies (GAs) individually in major disease hosts (families Acroporidae and Poritidae), were not significantly reduced within MPAs.

Effects of AMD3100 on transmigration and survival of acute myelogenous leukemia cells.

Acute myelogenous leukaemia (AML) blasts transmigrate in response to SDF-1alpha. AMD3100, a novel bicyclam molecule which inhibits stromal-derived factor (SDF)-1alpha/CXCR4 interactions, inhibited the transmigration of AML blasts and inhibited outgrowth of leukemia colony forming units. AMD3100 did not abrogate stroma-mediated protection from cytarabine-mediated apoptosis, except in the case of one promyelocytic leukemic sample tested, and it did not influence adhesion of blasts to endothelial monolayers.

Acute myelogenous leukemia--microenvironment interactions: role of endothelial cells and proteasome inhibition.

How leukemia progenitors interact with marrow microenvironment components is poorly understood. In this work, the effects of endothelial coculture on acute myelogenous leukemia (AML) blast survival is examined as are the effects of endothelial coculture on the impact of a cytotoxic agent such as cytarabine. Similar to marrow stromal cells, endothelial cells are able to increase survival and proliferation of AML blasts and to partially protect against cytarabine effects.

Coral diseases on Philippine reefs: genus Porites is a dominant host.

While it is generally assumed that Indo-Pacific reefs are not widely affected by diseases, limited data suggest a number of diseases and syndromes that appear to differ from those currently under study in the Caribbean. This report presents the results of a baseline survey of coral diseases in 2 regions in the Philippines: the Central Visayas and the Lingayen Gulf. Mean prevalence for all diseases observed was 8.

Effects of the farnesyl transferase inhibitor R115777 on normal and leukemic hematopoiesis.

Patients with acute myelogenous leukemia or myelodysplastic syndrome may respond to farnesyl transferase inhibitors (FTIs) with partial or complete response rates noted in about 30% of such patients. FTIs prevent the attachment of a lipid farnesyl moiety to dependent proteins prior to their insertion into the plasma membrane and thereby prevent activity of these prenylation-dependent proteins, but their mechanism of tumor suppression remains unknown. Many patients receiving FTIs do experience myelosuppression.

A phase I trial of immunotherapy with intratumoral adenovirus-interferon-gamma (TG1041) in patients with malignant melanoma.

Aims: Interferon-gamma (IFN-gamma) has been shown to upregulate MHC class I and II expression, and to promote generation of specific antitumor immune responses. We hypothesized that intratumoral administration of an IFN-gamma gene transfer vector facilitates its enhanced local production and may activate effector cells locally. We conducted a phase I dose-escalation study of a replication-deficient adenovirus-interferon-gamma construct (TG1041) to determine safety and tolerability of intratumoral administration, in advanced or locally recurrent melanoma.

Flavonoid effects on normal and leukemic cells.

Quercetin and flavopiridol, both flavonoids which influence oxidative milieu, proliferation, and apoptosis of various cell types, were examined for their effects on acute myelogenous leukemic cells and normal progenitors. Both quercetin and flavopiridol inhibited the growth and viability of various acute myelogenous leukemia (AML) cell lines and AML blasts isolated afresh from patients with AML of various subtypes. The effects on inhibition of proliferation and decreased viability were also significant in normal CD34+ cells isolated from normal marrow donors.

Response of human CD34+ cells to CXC, CC, and CX3C chemokines: implications for cell migration and activation.

Ultrastructural studies of marrow and examination of the in vivo processes of stem cell homing and mobilization show that multipotential hematopoietic progenitors are able to traverse endothelial cells. The regulation of this process by various classes of chemokines was studied in this report, using an in vitro model of transendothelial migration. Human umbilical vein endothelial cells (HUVECs) or bone marrow-derived endothelial cells (BMECs) were grown to confluence on 3-microm microporous membrane inserts and placed in 24-well culture plates.

Flavopiridol induces apoptosis and caspase-3 activation of a newly characterized Burkitt's lymphoma cell line containing mutant p53 genes.

Burkitt's lymphoma cell lines have been important in vitro models for studying the pathogenesis of Burkitt's lymphoma (BL) and for exploring new treatment strategies. A new EBV(-) Burkitt's lymphoma cell line (GA-10) was established from a patient with a clinically aggressive, chemorefractory BL and characterized. Although functional p-glycoprotein could not be demonstrated by dye-efflux assays, both p53 genes were mutated in the GA-10 cells, perhaps contributing to the resistant phenotype of the original neoplasm.

MIP-1alpha and TGF-beta production in CD34+ progenitor-stromal cell coculture systems: effects of progenitor isolation method and cell-cell contact.

ABSTRACT Macrophage inflammatory protein-1alpha (MIP-1alpha) is a C-C chemokine which has antiproliferative effects on early hematopoietic progenitors and stimulatory effects on later progenitors. It also possesses chemotactic and activating properties for monocytes, macrophages, and T-cells. CD34+ progenitors isolated utilizing an avidin-biotin immunoadsorption column produced significant amounts of MIP-1alpha from 24 h onward when cultured in medium with 10% fetal calf serum (>200 pg/ml).

A RANTES-antibody fusion protein retains antigen specificity and chemokine function.

The successful eradication of cancer cells in the setting of minimal residual disease may require targeting of metastatic tumor deposits that evade the immune system. We combined the targeting flexibility and specificity of mAbs with the immune effector function of the chemokine RANTES to target established tumor deposits. We describe the construction of an Ab fusion molecule with variable domains directed against the tumor-associated Ag HER2/neu, linked to sequences encoding the chemokine RANTES (RANTES.

Effect of stromal cell coculture on progenitor cell expansion and myeloid effector function in vitro.

Stimulation of CD34(+)-enriched marrow or light density marrow with various growth factor combinations can generate granulocyte progenitors and mature neutrophils in vitro. In this work, we have examined the influence of irradiated marrow stromal layers on growth factor-induced myeloid and early multipotential progenitor expansion from enriched marrow CD34+ progenitors. We have also explored whether the addition of early-acting growth factors known to enhance myelopoiesis in long-term culture, such as fibroblast growth factor (b-FGF), insulin growth factor (IGF-1), c-kit ligand or stem cell factor (SCF), and flk-2flt-3 ligand (FL), can lengthen survival of CD34+ progenitors in these cultures.

Structural elucidation of the capsular polysaccharide of Streptococcus pneumoniae type 9N.

The specific capsular polysaccharide of Streptococcus pneumoniae type 9N (American type 9) contains D-glucose, D-glucuronic acid, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D-mannose in the molar ratio of 2:1:1:1. Accumulated data from spectroscopic (13C and 1H nuclear magnetic resonance) and methylation analyses of the native and specifically degraded polysaccharide indicated that it was linear and composed of the following pentasaccharide repeating unit; -4)-alpha-D-GlcpA-(1 leads to 3)-alpha-D-Glcp-(1 leads to 3)-beta-D-ManpNAc-(1 leads to 4)-alpha-D-Glcp-(1 leads to 4)-beta-D -GlcpNAc(1 leads to. Structural regions in the type 9N polysaccharide common to those of types 9A, 9L, and 9V have been identified which account for the cross-reactivity of this groups of polysaccharides.

Structure of the 3-deoxy-D-manno-octulosonic acid-containing polysaccharide (K6 antigen) from Escherichia coli LP 1092.

The acidic polysaccharide (K6) antigen from Escherichia coli LP 1092 contains D-ribose and 3-deoxy-D-manno-octulosonic acid in the molar ratio of 2:1, respectively. Spectroscopic data (13C- and 1H-n.m.

Structure and serology of the native polysaccharide antigen of type Ia group B streptococcus.

The native polysaccharide antigen isolated from type Ia group B Streptococcus by using pH-controlled growth conditions and extraction procedures contains D-galactose, D-glucose, 2-acetamido-2-deoxy-D-glucose, and sialic acid in the molar ratio of 2:1:1:1. The structure of the native type Ia antigen has been elucidated; it can be represented by the following repeating unit in which all the side-chain beta-D-galactopyranose units are masked by sialic acid residues: [Formula: see text] Removal of all the sialic acid groups yields the incomplete type Ia polysacharide antigen with exposed terminal beta-D-galactopyranose residues. Antisera to type Ia organisms produced in rabbits according to the Lancefield procedures contain antibodies specific for both the native and incomplete antigens.