Fighting for recovery on multiple fronts: The past, present, and future of clinical trials for spinal cord injury.

Through many decades of preclinical research, great progress has been achieved in understanding the complex nature of spinal cord injury (SCI). Preclinical research efforts have guided and shaped clinical trials, which are growing in number by the year. Currently, 1,149 clinical trials focused on improving outcomes after SCI are registered in the U.

Speciation of Phosphorus from Agricultural Muck Soils to Stream and Lake Sediments.

The nature and management of agricultural soils can influence the forms of legacy P present in affected sediments; however, few studies have specifically characterized P in sediments affected by polder agriculture. In this study, the speciation of P as it flows from the muck soils of the Holland Marsh to the sediments of the West Holland River and Lake Simcoe, Ontario, Canada, was investigated. The distribution of P fractions and the characterization of organic P were analyzed by the sequential fractionation method and solution P nuclear magnetic resonance spectroscopy, respectively.

Philadelphia Chromosome Symposium: commemoration of the 50th anniversary of the discovery of the Ph chromosome.

This report summarizes highlights of the Philadelphia Chromosome Symposium: Past, Present and Future, held September 28, 2010, to commemorate the 50th anniversary of the discovery of the Philadelphia chromosome. The symposium sessions included presentations by investigators who made seminal contributions concerning the discovery and molecular characterization of the Ph chromosome and others who developed a highly successful therapy based on the specific molecular alteration observed in chronic myeloid leukemia. Additional presentations highlighted future opportunities for the design of molecularly targeted therapies for various types of cancer.

Trisomy 8 in an allogeneic stem cell transplant recipient representative of a donor-derived constitutional abnormality.

Trisomy 8 is a common cytogenetic abnormality in myeloid malignancies. It can also be present constitutionally and is associated with a wide range of phenotypes. We report a case of a 20-year-old woman with acute myelogenous leukemia associated with the 11q23/MLL translocation who underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a healthy, unrelated 26-year-old female.

Sézary syndrome coexisting with B-cell chronic lymphocytic leukemia: case report and review of the literature.

Introduction: The simultaneous presentation of chronic B-cell lymphocytic leukemia (B-CLL) and cutaneous T-cell lymphoma (CTCL) is extremely rare.

Case Report: We describe a patient with B-CLL and Sézary syndrome (SS), an erythrodermic and leukemic variant of CTCL. Despite treatment, the SS progressed to involve internal organs and eventual death of the patient from sepsis.

Relationships between REM sleep findings and PTSD symptoms during the early aftermath of trauma.

Laboratory sleep findings in posttraumatic stress disorder (PTSD) have been characterized as incongruent with subjective complaints. Most findings relate to rapid eye movement (REM) sleep. Chronicity confounds relationships between objective sleep and PTSD.

Discovery of the Philadelphia chromosome: a personal perspective.

Almost 50 years ago, David Hungerford and I noticed an abnormally small chromosome in cells from patients with chronic myelogenous leukemia (CML). This article is a personal perspective of the events leading to the discovery of this chromosome, which became known as the Philadelphia chromosome. As technology advanced over subsequent decades, the translocation resulting in the Philadelphia chromosome has been identified, its role in the development of CML has been confirmed, and a therapy directed against the abnormal protein it produces has shown promising results in the treatment of patients with CML.

Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with the retinoid X receptor agonist bexarotene.

All-trans-retinoic acid has dramatically changed the treatment paradigm for acute promyelocytic leukemia, however, it has no significant activity in non-M3 acute myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist inhibits the proliferation of non-M3 AML cell lines and induces differentiation of leukemic blasts from patients. We hypothesized that there may be similar activity in patients with AML.

A novel t(3;8)(q27;q24.1) simultaneously involving both the BCL6 and MYC genes in a diffuse large B-cell lymphoma.

Diffuse large B-cell lymphomas (DLBCLs) are a clinically and biologically heterogeneous group of hematologic malignancies. Specific genetic aberrations underlie some of this heterogeneity. These genetic events include distinct and separate translocations resulting in the dysregulated expression of either BCL6 protein with the t(3;14)(q27;q32) or c-MYC protein with the t(8;14)(q24;q32), as a consequence of the juxtaposition of these oncogenes with heterologous promoters or enhancers, such as those of the immunoglobulin heavy chain gene.

Sézary cell counts in erythrodermic cutaneous T-cell lymphoma: implications for prognosis and staging.

In this retrospective study, quantitative Sézary cell counts were performed at presentation on 192 patients with erythrodermic cutaneous T-cell lymphoma (E-CTCL). Per recommendation of the International Society of Cutaneous Lymphomas (ISCL), the impact on staging of using an absolute Sézary cell count of 1.0 K microL-1 or more as equivalent to lymph node involvement was investigated.

Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity.

The prognosis for patients with mantle cell lymphoma (MCL) is poor, and at present there is no truly effective therapy. Gene translocation-mediated constitutive expression of cyclin D1 seems to play the key role in the pathogenesis of MCL. Here we report that although 3 of 4 MCL cell lines expressed the recently identified, highly oncogenic cyclin D1b isoform, as well as the canonical cyclin D1a, 8 MCL patient samples expressed only the cyclin D1a protein despite expressing detectable cyclin D1b mRNA.

Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell lymphomas suggesting impaired cell cycle control in disease pathogenesis.

Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray.

A meta-regression to examine the relationship between aerobic fitness and cognitive performance.

Many studies have been conducted to test the potentially beneficial effects of physical activity on cognition. The results of meta-analytic reviews of this literature suggest that there is a positive association between participation in physical activity and cognitive performance. The design of past research demonstrates the tacit assumption that changes in aerobic fitness contribute to the changes in cognitive performance.

Insomnia.

Effective management of insomnia begins with recognition and adequate assessment. Family doctors and other health care providers such as practice nurses and psychologists should routinely enquire about sleep habits as a component of overall health assessment. Identification and treatment of primary psychiatric disorders, medical conditions, circadian disorders, or specific physiological sleep disorders--eg, sleep apnoea and periodic limb movement disorder--are essential steps in management of insomnia.

BCL2 and JUNB abnormalities in primary cutaneous lymphomas.

Background: BCL2 is upregulated in nodal and extranodal B-cell non-Hodgkin's lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis.

Objectives: To investigate genomic and protein expression status of BCL2 and to compare the results with that of JUNB in primary cutaneous lymphomas (PCLs).

Headache complaints in relation to nocturnal oxygen saturation among patients with sleep apnea syndrome.

Background: Morning headaches are often ascribed to patients with sleep apnea syndrome (SAS) but the etiology of headaches in SAS is unclear. Given the relationship between oxygen and other headache syndromes, nocturnal hypoxia might be one factor contributing to headaches in SAS.

Methods: All subjects 18-80 years of age who were determined to have SAS and who underwent a continuous positive airway pressure trial in our sleep laboratory between March 1, 1997 and March 18, 1998 were considered for inclusion.

Multiplex RT-PCR for the detection of leukemia-associated translocations: validation and application to routine molecular diagnostic practice.

The aim of this study was to validate the application of a commercially available multiplex reverse transcription polymerase chain reaction (RT-PCR) assay [Hemavision-7 System] for the seven most common leukemia translocations for routine molecular diagnostic hematopathology practice. A total of 98 samples, comprising four groups, were evaluated: Group 1, 16 diagnostic samples molecularly positive by our existing laboratory-developed assays for PML-RARalpha/t (15;17) or BCR-ABL/t (9;22); Group 2, 51 diagnostic samples negative by our laboratory-developed assays for PML-RARalpha/t (15;17) or BCR-ABL/t (9;22); Group 3, 21 prospectively analyzed diagnostic cases, without prior molecular studies; and Group 4, 10 minimal residual disease (MRD) samples. Analysis of the two previously studied cohorts (Groups 1 and 2) confirmed the diagnostic sensitivity and specificity of the multiplex assay with regard to these two translocations.

Management of health-care--associated infections in the oncology patient.

Each year, 2.4 million patients in the United States develop health-care--associated infections (HAIs), requiring treatment at an annual cost of approximately $4.5 billion.

Diminished expression of the type II receptor for TGFbeta (TGFbetaRII) in T lymphocytes from patients with Sezary syndrome is not due to mutations in the receptor's poly-A tract: limitations of the standard RT-PCR in cDNA sequence analysis of homopolymeric base stretches.

Peripheral blood lymphocytes from patients with Sezary syndrome (SzS) frequently demonstrate decreased surface expression of transforming growth factor beta receptor II (TGFbetaRII). The mechanism of this low TGFbetaRII expression remains unknown. Because mutations within the poly-A tract of the TGFbetaRII sequence (nucleotides 709-718) were shown to result in diminished TGFbetaRII expression in other types of malignant tumors, we examined the sequence of the TGFbetaRII poly-A tract in two SzS-derived cell lines and in peripheral blood SzS cells from 17 SzS patients and 4 control, healthy individuals using DNA sequencing and single-stranded conformation polymorphism (SSCP) analysis.

Unusually indolent T-cell prolymphocytic leukemia associated with a complex karyotype: is this T-cell chronic lymphocytic leukemia?

T-cell prolymphocytic leukemia (T-PLL) is typically associated with an aggressive clinical course, with a median survival of less than 1 year. We report a case of T-PLL that displays multiple cytogenetic abnormalities, with the most complex subclone having the following karyotype: 47, Y, -X, +8, inv (10) (p12q26), del (11) (p13p15) +marker. However, despite this genetic complexity, the leukemia has behaved in a remarkably indolent manner, with the patient remaining asymptomatic, without therapeutic intervention, for more than 7 years.

Low NAD(P)H:quinone oxidoreductase activity is associated with increased risk of leukemia with MLL translocations in infants and children.

An inactivating polymorphism at position 609 in the NAD(P)H:quinone oxidoreductase 1 gene (NQO1 C609T) is associated with an increased risk of adult leukemia. A small British study suggested that NQO1 C609T was associated with an increased risk of infant leukemias with MLL translocations, especially infant acute lymphoblastic leukemia (ALL) with t(4;11). We explored NQO1 C609T as a genetic risk factor in 39 pediatric de novo and 18 pediatric treatment-related leukemias with MLL translocations in the United States.

Studies of normal and neoplastic lymphocytes.

This brief review encapsulates a nearly 50-year career in biomedical research, primarily studying human leukemias and lymphomas, but also involving normal lymphocytes. Early observations included the feasibility of bone marrow transplantation (and related problems with graft-vs.-host reactions); the mitogenic effect of phytohemagglutinin (and resultant human lymphocyte culture techniques); and early cytogenetic findings in human leukemias, both lymphocytic and myeloid (including the Philadelphia chromosome).

Tumor progression: a brief historical perspective.

It has long been known that tumors become more clinically and biologically aggressive over time. This has been termed 'tumor progression' and includes, among other properties invasion and metastasis, as well as more efficient escape from host immune regulation. Since 1960, first cytogenetics and then molecular techniques have shown that tumors expand as a clone from a single altered cell, and that clinical 'progression' is the result of sequential somatic genetic changes, generating increasingly aggressive subpopulations within the expanding clone.

Panhandle and reverse-panhandle PCR enable cloning of der(11) and der(other) genomic breakpoint junctions of MLL translocations and identify complex translocation of MLL, AF-4, and CDK6.

We used panhandle PCR to clone the der(11) genomic breakpoint junction in three leukemias with t(4;11) and devised reverse-panhandle PCR to clone the breakpoint junction of the other derivative chromosome. This work contributes two elements to knowledge on MLL translocations. First is reverse-panhandle PCR for cloning breakpoint junctions of the other derivative chromosomes, sequences of which are germane to understanding the MLL translocation process.