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Biomedical subjects

J E Anderson

Publications and source records attributed to J E Anderson.

At least 91 records · Page 5Linked to original sources

Lower left temporal lobe MRI volumes in patients with first-episode schizophrenia compared with psychotic patients with first-episode affective disorder and normal subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies of schizophrenic patients have revealed structural brain abnormalities, with low volumes of gray matter in the left posterior superior temporal gyrus and in medial temporal lobe structures. However, the specificity to schizophrenia and the roles of chronic morbidity and neuroleptic treatment in these abnormalities remain unclear. METHOD: Magnetic resonance (1.5-T) scans were obtained from 33 patients with first-episode psychosis and 18 age-matched normal comparison subjects, all right-handed. Sixteen of the patients were diagnosed with affective disorder and 17 with schizophrenia. RESULTS: Quantitative volumetric analysis showed that the patients with first-episode schizophrenia had significantly smaller gray matter volume in the left posterior superior temporal gyrus than did the patients with first-episode affective psychosis or the comparison subjects, with a significant left-less-than-right asymmetry. The schizophrenic patients also showed a smaller gray matter volume of the left posterior amygdala-hippocampal complex than the comparison subjects. Both the patients with schizophrenia and those with affective psychosis had significant left-less-than-right asymmetry of the posterior amygdala-hippocampal complex. CONCLUSIONS: These findings suggest that temporal lobe abnormalities are present at the first hospitalization for schizophrenia and that low volume of the left posterior superior temporal gyrus gray matter is specific to schizophrenia compared with affective disorder.

Adolescent↗

Levels of MyoD protein expression following injury of mdx and normal limb muscle are modified by thyroid hormone.

Thyroid hormone (T3) affects muscle development and muscle regeneration. It also interacts with the muscle regulatory gene MyoD in culture and affects myoblast proliferation. We studied the localization of MyoD protein using a well-characterized polyclonal antibody for immunohistochemistry. Relative numbers of myogenic precursor cells per field were identified by their MyoD expression during muscle regeneration in normal and mdx dystrophic mice, with particular reference to the expression in mononuclear cells and myotubes at various T3 levels. In regeneration by normal muscles, relatively few MyoD+ nuclei per field were present in mononuclear cells of euthyroid and hypothyroid mice. MyoD staining of mononuclear cell nuclei was approximately doubled in fields of regenerating muscles of normal hyperthyroid compared to euthyroid mice, and was observed in precursors that appeared to be aligned before fusion into myotubes. In mdx regenerating muscle, twofold more mononuclear cells positive for MyoD were present in all three treatment groups compared to normal muscles regenerating under the same conditions. Localization was similar to the pattern in normal euthyroid mice. However, in muscles regenerating in hyperthyroid mdx mice, both mononuclear cell nuclei and centrally located nuclei in a subpopulation (about 15%) of new myotubes formed after the crush injury were intensely stained for MyoD protein. The changes observed are consistent with reports on T3-induced alteration of muscle repair, and propose a link between MyoD regulation and the accelerated differentiation during regeneration under high T3 conditions. (J Histochem Cytochem 46:59-67, 1998)

Animals↗

Telephone coverage and measurement of health risk indicators: data from the National Health Interview Survey.

OBJECTIVES: This study compared health behavior variables for all US households and households with telephones to measure the potential impact of telephone coverage on estimates from telephone surveys. METHODS: Data were derived from the 1991 through 1994 version of the National Health Interview Survey. RESULTS: Ninety-five percent of respondents lived in households with telephones. Differences in health indicators were small (< 1%) in comparisons between all households and those with telephones. Results were similar when only respondents below the poverty level were included. CONCLUSIONS: Telephone noncoverage effects appear to be small, supporting the use of telephone surveys for health risk behavior surveillance with most population groups.

Adult↗

Progressive changes in schizophrenia: do they exist and what do they mean?

Schizophrenia is a disorder characterized by multiple symptoms, with a varied course and outcome. The etiology is yet unknown, but multiple pathological processes or, equally likely, a unique pathophysiological process, may be involved. Here, we review evidence for progressive changes in schizophrenia in order to understand further the pathophysiology of this disorder. We first present evidence for clinical and psycho-social changes over time, followed by evidence from structural brain studies that suggests that schizophrenia is a brain disorder. We then review findings from the small number of longitudinal studies that have evaluated structural brain changes in schizophrenia, followed by a review of the evidence for neurophysiological changes, both cross-sectional and longitudinal. This is followed by a discussion of possible cellular mechanisms, including NMDA receptor abnormalities, that might account for structural and functional brain changes (temporal and frontal), and we discuss how these abnormalities might be related to not only the specific signs and symptoms of schizophrenia but also to the onset and course of the illness. Finally, we discuss neurodevelopment (static and perhaps non-static alterations) and neurodegenerative theories of schizophrenia. We propose that the two are not mutually exclusive, but instead likely reflect a "two-hit" model for some subtypes of schizophrenia.

Journal Article↗

Murray L. Barr Award Lecture. Studies of the dynamics of skeletal muscle regeneration: the mouse came back!

Regeneration of skeletal muscle tissue includes sequential processes of muscle cell proliferation and commitment, cell fusion, muscle fiber differentiation, and communication between cells of various tissues of origin. Central to the process is the myosatellite cell, a quiescent precursor cell located between the mature muscle fiber and its sheath of external lamina. To form new fibers in a muscle damaged by disease or direct injury, satellite cells must be activated, proliferate, and subsequently] fuse into an elongated multinucleated cell. Current investigations in the field concern modulation of the effectiveness of skeletal muscle regeneration, the regeneration-specific role of myogenic regulatory gene expression distinct from expression during development, the impact of growth and scatter factors and their respective receptors in amplifying precursor numbers, and promoting fusion and maturation of new fibers and the ultimate clinical therapeutic applications of such information to alleviate disease. One approach to muscle regeneration integrates observations of muscle gene expression, proliferation, myoblast fusion, and fiber growth in vivo with parallel studies of cell cycling behaviour, endocrine perturbation, and potential biochemical markers of steps in the disease-repair process detected by magnetic resonance spectroscopy techniques. Experiments on muscles from limb, diaphragm, and heart of the mdx dystrophic mouse, made to parallel clinical trials on human Duchenne muscular dystrophy, help to elucidate mechanisms underlying the positive treatment effects of the glucocorticoid drug deflazacort. This review illustrates an effective combination of in vivo and in vitro experiments to integrate the distinctive complexities of post-natal myogenesis in regeneration of skeletal muscle tissue.

Animals↗

A patient-oriented approach to treatment of myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: There are several therapeutic options for patients with myeiodysplastic syndrome (MDS) but most of them are poorly effective and the potentially curative ones are available only for a minority of individuals. The aim of this article is to define a rational basis for a patient-oriented approach to treatment of MDS. EVIDENCE AND INFORMATION SOURCES: All four authors have done clinical studies of treatment of MDS, including stem cell transplantation, intensive and low-dose chemotherapy, and use of hematopoietic growth factors. They also participated in the Fourth international Symposium on MDS (Barcelona, 24-27 April 1997). In addition, the present review critically examines relevant articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART AND PERSPECTIVES: At present, the only two treatments that can prolong survival are allogeneic stem cell transplantation (SCT) and intensive chemotherapy, but only a minority of MDS patients can really benefit from them. The heterogeneity of MDS patients, the wide variety of patient inclusion criteria and transplant procedures used, and relatively small numbers of patients in the individual reports of allogeneic SCT make it difficult to draw many definitive conclusions. However, approximately 40% of patients with MDS who are eligible for allogeneic SCT are likely to be cured by this treatment. Intensive chemotherapy with a combination of cytosine arabinoside and an anthracycline should be offered to all patients with an increase in bone marrow blasts who are not eligible for allogeneic SCT, especially those patients up to 65 years of age. Complete remission rates are similar to those obtained in patients with acute myelogenous leukemia, but probability of long-term survival is low. The remaining treatments validated in clinical trials (erythropoietin and/or granulocyte colony-stimulating factor, low-dose cytosine arabinoside) can improve the efficiency of hematopoiesis in subsets of patients. Responsive individuals might experience an improvement in quality of life but very few studies have addressed this question so far. The majority of MDS patients still rely upon supportive therapy. A clinical decision path based on findings of clinical trials and the patient's expectations can help physicians in decision making. Because of the inadequacies of all current treatment modalities, participation in clinical trials should always be encouraged.

Antineoplastic Combined Chemotherapy Protocols↗

State-and sex-specific prevalence of selected characteristics--behavioral risk factor surveillance system, 1994 and 1995.

PROBLEM/CONDITION: High-risk behaviors (e.g., cigarette smoking, excessive alcohol consumption, and physical inactivity) and lack of preventive health care (e.g., screening for cancer) are associated with chronic disease- and injury-related morbidity and mortality. States use the Behavioral Risk Factor Surveillance System (BRFSS) to collect data about these modifiable health behaviors and to monitor trends and changes in the prevalence of behavioral risk factors in state populations. BRFSS data also are used to monitor progress toward the year 2000 national health objectives. REPORTING PERIOD: 1994 and 1995. DESCRIPTION OF SYSTEM: The BRFSS is a state-based telephone survey of the civilian, noninstitutionalized, adult (persons > or =18 years of age) population. In 1994, 49 states and the District of Columbia participated in the BRFSS; in 1995, 50 states participated. RESULTS: As in previous years, there were state-specific variations in the prevalences of high-risk behaviors, awareness of certain medical conditions, use of preventive health services, and health-care coverage. Selected findings for 1995 were that 22.4% of adults reported being current cigarette smokers (range: 13.2%-27.8%); the percentage of adults who reported driving after drinking too much alcohol ranged from 0.6% to 5.2% (median: 2.3%); and among adults aged > or =65 years, 36.8% (range: 11.4%-46.6%) reported ever having had a pneumococcal vaccination and 59.2% (range: 44.2%-70.0%) reported having had an influenza vaccination within the past 1 year. INTERPRETATION: State-specific variations in prevalence may reflect differences in population composition, socioeconomic factors, state laws enacted to discourage high-risk behaviors, levels of effort to screen for certain diseases and physiological conditions, and other factors. ACTION TAKEN: States continue to use the BRFSS to monitor risk factors associated with chronic disease- and injury-related morbidity and mortality and to develop public health programs and policies to address these problems. BRFSS data continue to be important in assessing progress toward national year 2000 and state health objectives.

Adult↗

Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy.

The purpose of this report is to describe the results of stem cell transplantation as initial treatment for secondary acute myeloid leukemia (AML). Forty-six patients (median age 42 years) with secondary AML (17 therapy-related, 29 myelodysplasia-related) who had not received remission induction chemotherapy underwent allogeneic (n = 43) or syngeneic (n = 3) transplantation. The 5-year actuarial disease-free survival was 24.4%, and the cumulative incidences of relapse and nonrelapse mortality were 31.3% and 44.3%, respectively. Lower peripheral blood blast count was associated with a lower risk of relapse (P = .05) and shorter time from AML diagnosis to transplant was associated with a lower risk of nonrelapse mortality (P = .02) and improved disease-free survival (P = .026). Patients with therapy-related secondary AML tended to have lower disease-free survival (P = .16) and a higher relapse rate (P = .16) than patients whose leukemia was not therapy-related. The results of these 46 previously untreated patients were compared to 20 patients (median age 36 years, 12 therapy-related, 8 myelodysplasia-related) transplanted with chemotherapy-sensitive disease after induction chemotherapy (first complete remission [n = 6], second complete remission [n = 3], first untreated relapse [n = 11]). We found no statistically significant difference in outcome between these 2 groups of patients. These results suggest that prompt transplantation should be considered after diagnosis of secondary AML or, if possible, high-risk myelodysplasia, particularly in patients with low peripheral blast counts. Innovative transplant strategies are needed to reduce the high risks of relapse and nonrelapse mortality seen in this patient population.

Adolescent↗

Allogeneic marrow transplantation for primary myelofibrosis and myelofibrosis secondary to polycythaemia vera or essential thrombocytosis.

Primary myelofibrosis is a clonal haemopoietic disorder, incurable with conventional therapy, and associated with a median survival of 4-5 years. Patients with polycythaemia vera and essential thrombocytosis who progress into a myelofibrotic picture also have a poor prognosis. Between 1980 and 1996, 13 patients with myelofibrosis due to one of these three myeloproliferative disorders (primary myelofibrosis [n=8], essential thrombocytosis [n=3], polycythaemia vera [n=2]) underwent allogeneic marrow transplantation in Seattle. The median age was 40 years (range 18-49). The median time from myeloproliferative diagnosis to transplantation was 39 months (range 5-192). Three patients received preparative regimens containing total body irradiation and 10 received busulphan-cyclophosphamide regimens. Nine patients received marrow from HLA-matched related donors, one from a one antigen mismatched related donor, and three from HLA-matched unrelated donors. The median time to both granulocyte and platelet engraftment was 21 d. Nine patients survive between 1.2 and 7.1 years post-transplant. Two patients relapsed at 1 year post-transplant, both of whom survive in a chronic myeloproliferative state. Four patients died of transplant-related complications between 43 d and 2.2 years post-transplant. At 1 year post-transplant the majority of the disease-free survivors have normal peripheral blood counts and none-to-minimal marrow fibrosis. These preliminary results are encouraging, and suggest that stem cell transplantation can be curative therapy for selected patients with myelofibrosis.

Adolescent↗

Cloning and functional characterization of Neisseria gonorrhoeae tonB, exbB and exbD genes.

Neisseria gonorrhoeae is able to utilize iron (Fe) from a variety of sources including transferrin (TF) and lactoferrin (LF). To gain insight into the molecular mechanisms used by gonococci to scavenge Fe from TF and LF, we cloned a 3.5 kb segment of wild-type DNA that repaired the defect in tlu mutants, which are unable to take up Fe from either TF or LF despite exhibiting apparently normal ligand binding to the receptor. Nucleotide sequence determination identified three open reading frames (ORFs), designated ORF1, ORF2, and ORF3, which were arranged in tandem. The deduced amino acid sequence of the 852 bp ORF1 encoded a 28 kDa protein that exhibited 26-32% identity with TonB proteins of nine other bacteria. The 663 bp ORF2 predicted a 24 kDa protein and the 435 bp long ORF3 predicted a 15 kDa protein. These predicted protein sequences exhibited 32-38% and 24-36% identity, respectively, with ExbB and ExbD proteins of three other bacteria. Thus, the sequence comparison identified the ORF1, ORF2 and ORF3 as gonococcal homologues of the E. coli tonB, exbB and exbD genes. An insertional mutation in the tonB homologue resulted in the failure of gonococci to grow with TF, LF or human haemoglobin (HB) as sole Fe sources and in the inability to take up 55Fe from TF and LF. The tonB mutation did not prevent the utilization of Fe from citrate (CT) or haemin (HM). Binding of TF, LF and HB to whole cells in a solid-phase binding assay was largely unaffected by the tonB mutation. We conclude that the pathways for utilization of Fe bound to TF, LF and HB but not to HM or CT were dependent on the TonB system.

Bacterial Proteins↗

Energy-dependent changes in the gonococcal transferrin receptor.

The pathogenic Neisseria spp. are capable of iron utilization from host iron-binding proteins including transferrin and lactoferrin. Transferrin iron utilization is an energy-dependent, receptor-mediated event in which two identified transferrin-binding proteins participate. One of these proteins, TbpA, is homologous to the TonB-dependent family of outer membrane receptors that are required for high-affinity uptake of vitamin B12 and ferric siderophores. The 'TonB box' is a conserved domain near the amino-terminus of these proteins that has been implicated in interaction with TonB. Interaction between a periplasmic domain of TonB and the TonB box allows energy transduction to occur from the cytoplasmic membrane to the energy-dependent receptor in the outer membrane. We created a TonB box mutant of gonococcal TbpA and demonstrated that its binding and protease accessibility characteristics were indistinguishable from those of gonococcal Ton system mutants. The protease exposure of the second transferrin-binding protein, TbpB, was affected by the energization of TbpA, consistent with an interaction between these proteins. TbpB expressed by the de-energized mutants was readily accessible to protease, similar to TbpB expressed in the absence of TbpA. The de-energized mutants exhibited a marked decrease in transferrin diffusion rate, suggesting that receptor energization was necessary for ligand release. We propose a model to explain the observed Ton-dependent changes in the binding parameters and exposures of TbpA and TbpB.

Bacterial Outer Membrane Proteins↗

Myelodysplasia and myeloproliferative disorders.

Myelodysplasia and the myeloproliferative disorders are clonal hematopoietic stem cell disorders with heterogeneous clinical presentations and prognoses. This review highlights some of the recent progress that has been made in these disorders. Specifically, a number of studies have enhanced our understanding of the pathogenesis of these disorders, and potentially useful animal models for primary myelofibrosis have been developed. New, clinically useful prognostic scoring systems have been devised for myelodysplasia and for primary myelofibrosis. New chemotherapeutic approaches and nonmyelosuppressive alternative therapies for myelodysplasia have been studied. Data on the use of interferon for polycythemia vera and the potential leukemogenesis of hydroxyurea have recently become available. Finally, continued progress has been made in the use of allogeneic (related and unrelated donor) and autologous stem cell transplantation for myelodysplasia.

Humans↗

Transformation yields of chlorinated ethenes by a methanotrophic mixed culture expressing particulate methane monooxygenase.

Transformation yields for the aerobic cometabolic degradation of five chlorinated ethenes were determined by using a methanotrophic mixed culture expressing particulate methane monooxygenase (pMMO). Transformation yields (expressed as moles of chlorinated ethene degraded per mole of methane consumed) were 0.57, 0.25, 0.058, 0.0019, and 0.00022 for trans-1,2-dichloroethylene (t-DCE), vinyl chloride (VC), cis-1,2-dichloroethylene (c-DCE), trichloroethylene (TCE), and 1,1-dichloroethylene (1,1-DCE), respectively. Degradation of t-DCE and VC was observed only in the presence of formate or methane, sources of reducing energy necessary for cometabolism. The t-DCE and VC transformation yields represented 35 and 15%, respectively, of the theoretical maximum yields, based on reducing-energy availability from methane dissimilation to carbon dioxide, exclusive of all other processes that require reducing energy. The yields for t-DCE and VC were 20 times greater than the yields reported by others for cells expressing soluble methane monooxygenase (sMMO). Transformation yields for c-DCE, TCE, and 1,1-DCE were similar to or less than those for cultures expressing sMMO. Although methanotrophic biotreatment systems have typically been designed to incorporate cultures expressing sMMO, these results suggest that pMMO expression may be highly advantageous for degradation of t-DCE or VC. It may also be much easier to maintain pMMO expression in treatment systems, because pMMO is expressed by all methanotrophs whereas sMMO is expressed only by type II methanotrophs under copper-limited conditions.

Bacteria↗

Characterization of the diversity and the transferrin-binding domain of gonococcal transferrin-binding protein 2.

The molecular weight heterogeneities of Tbp1 and Tbp2 among a panel of 45 gonococcal isolates were assessed. The tbpB genes from four of these strains were sequenced to characterize the Tbp2 sequence diversity among gonococci. By expressing truncated versions of gonococcal Tbp2, we delimited the extent of Tbp2 necessary for transferrin binding in a Western blot.

Amino Acid Sequence↗

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

Adolescent↗

Bioactive furonaphtoquinones from Tabebuia barbata (Bignoniaceae).

Tabebuia barbata (E. Mey) Sandw. (Bignoniaceae), locally known as "palo de arco", is indigenous to the upper Orinoco and Amazonas rivers. Brine shrimp lethality-directed fractionation and extensive column chromatography, normal-phase preparative TLC and normal-phase HPLC separation of the ethanol extract of the bark of this previously uninvestigated species has led to the isolation of five active compounds 1-5. The combined spectral evidence (UV, IR, 1H and 13C NMR and mass) identified these compounds as naphthoquinones. These compounds, characterized as lapachol (1), 2-acetylnaphtho-[2,3-b]-furan-4,9-dione (2), 2-acetyl-5-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (3), 2-acetyl-8-hydroxy-naphtho-[2,3-b]-furan-4,9-dione (4), and (+)-8-hydroxy-2(1-hydroxy-ethyl) naphtho-[2,3-b]-furan-4,9-dione (5), were reported previously from other species of the genus Tabebuia but not from T. barbata. Compounds 2-5, reference adriamycin, were significantly cytotoxic against A-549 human lung adeno-carcinoma, MCF-7 human breast carcinoma, and HT-29 human colon carcinoma cells. The compounds isolated (1-5) were also shown to be inhibitors of electron transport in rat liver mitochondria, reference to rotenone, with IC50 values in the range of 15 microM to 82.5 microM. In addition, this study demonstrated that screening and activity-directed fractionation, using brine shrimp lethality as a simple and inexpensive bioassay, can effectively lead to potential antitumor compounds.

Animals↗