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PubMed2005

Surveillance and the Tao of leadership: a perspective from the United States.

This paper discusses how the epidemiologists who guide the collection, analysis, and sharing of public health data are powerful and can use their influence to bring about changes that will benefit the health of people around the world. They can frame public debate and the actions of policy makers on major health issues because they have the power to determine what health indicators are measured, which questions are asked, and how the raw data are presented. To be effective leaders, these epidemiologists can learn much from the ancient Chinese philosophy of the Tao Te Ching, which advises powerful people to lead others without domination or coercion.

Adult↗
PubMed2000

Progesterone receptor expression in orbital cavernous hemangiomas.

Orbital cavernous hemangiomas (OCH) have thick and highly cellular vascular walls. Ultrastructural studies have demonstrated the smooth muscle nature of these cells. Vascular neoplasms can modify their morphological and clinical features under hormonal stimulation. The purpose of the present study was to investigate the presence of smooth muscle markers and sex steroid receptors in 12 cases of OCH. Orbital cases were compared with cutaneous hemangiomas and subcutaneous angioleiomyomas. Smooth muscle actin (SMA) and desmin were localized in spindle cells of the vascular walls of all 12 cases studied. OCH showed immunohistochemical positivity with progesterone receptor (PR) antibody both in smooth muscular and in endothelial cells. For comparison, sex steroid receptors were studied in 10 cases of cutaneous cavernous hemangioma and in 10 cases of subcutaneous angioleiomyoma. PR was found in smooth muscle and endothelial cells of 6 out of 10 cases of subcutaneous angioleiomyoma and in none of the cases of cutaneous cavernous hemangioma. No positivity was obtained with estrogen receptor (ER) antibody in any of the cases tested. The present data suggest that OCH share morphological and immunohistochemical features with subcutaneous angioleiomyomas. Furthermore, immunohistochemical positivity with PR antibody indicates that OCH have to be added to the list of mesenchymal lesions that express sex steroid receptors.

Adult↗
PubMed1983

Evidence for a carbanion intermediate in catalysis by spinach ribulose-1,5-bisphosphate carboxylase/oxygenase.

Spinach ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (EC 4.1.1.39) showed marked reactivity towards tetranitromethane in the presence of RuBP, when the enzyme was in the fully activated state. The inactivated enzyme did not catalyze substrate-dependent nitroform production. Nitroform production was proportional to the concentration of the enzyme and tetranitromethane at optimal substrate concentrations. The pH optimum for nitroform production was similar to that for carboxylation. The effects of bicarbonate, ribulose-1,5-bisphosphate, and temperature on partition of the intermediate between production of phosphoglycerate and nitroform indicate that both routes share a common intermediate. Data on stoichiometry of the reaction imply that the intermediate is not oxidized by tetranitromethane but instead is nitrated. The data are compatible with a carbanion intermediate in the reaction catalyzed by ribulose-1,5-bisphosphate carboxylase.

Anions↗
PubMed1985

Muramyl peptides and serotonin interact at specific binding sites on macrophages and enhance superoxide release.

Serotonin at low micromolar concentrations inhibited binding of two [125I]-labeled muramyl peptides to resident mouse peritoneal cells and to a macrophage-derived cell line, PU5-1.8-F7. Binding of [3H]serotonin was inhibited in parallel fashion. Overnight incubation with serotonin or muramyl peptide enhanced the release of superoxide by both types of cells when later stimulated with phorbol myristate acetate. Serotonin antagonists decreased binding of muramyl peptide and serotonin and diminished the subsequent enhancement of superoxide release. A cell line variant lacking detectable binding sites for muramyl peptide was far less responsive (superoxide release) than the parent line, to either drug. The data are consistent with sharing of a common set of receptors on the macrophage by muramyl peptide and serotonin and with involvement of these receptors in enhancing superoxide release.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1992

Recombination between similar but not identical DNA sequences during yeast transformation occurs within short stretches of identity.

Interactions between similar but not identical (homeologous) DNA sequences play an important biological role in the evolution of genes and genomes. To gain insight into the underlying molecular mechanism(s) of genetic recombination, we have studied inter- and intramolecular homeologous recombination in S. cerevisiae during transformation. We found that homeologous DNAs recombine efficiently. Hybrid sequences were obtained between two mammalian cytochrome P450 cDNAs, sharing 73% identity, and between the yeast ARG4 gene and its human homeologous cDNA, sharing 52% identity. Sequencing data showed that the preferred recombination events are those corresponding to the overall alignment of the DNA sequences and that the junctions are within stretches of identity of variable length (2-21 nt). We suggest that these events occur by a conventional homologous recombination mechanism.

Base Sequence↗
PubMed1992

Neurological consequences of immune dysfunction: lessons from HIV infection and multiple sclerosis.

In a recent workshop held on Sanibel Island, Florida (18-21 January 1992), the two most common neuroimmunologic diseases of young adults, multiple sclerosis (MS) and HIV encephalopathy, were jointly discussed. The logic of assembling investigators from these two fields was based not on an assumed etiologic connection between MS and retroviral infection of the central nervous system (CNS), but rather in the hope of uncovering potential common pathogenic mechanisms, particularly as might relate to trafficking of mononuclear cells into the central nervous system, the distribution and function of macrophages and microglia, the structure and function of the blood-brain barrier, and the role of cytokines released by activated cells. Multiple sclerosis is a disease without a known etiologic agent or pathogenesis. While the causative agent for HIV leukoencephalopathy is known, the pathogenesis of the disease remains entirely enigmatic (a topic covered by R. Johnson). This meeting brought together two different groups of investigators to compare and contrast the diseases and to share perspectives, paradigms, and data with the aim of cross-fertilizing the disciplines and generating healthy hybrids.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Radiation therapy treatment planning using concurrent programming.

Concurrent programming can be applied to the problem of computer graphic simulation of radiation treatment of tumors (radiation treatment planning). Running several tasks or programs simultaneously on behalf of a single user provides a big improvement over the traditional sequential approach, in which editing a treatment plan and computing and displaying dose distributions are separate operations which must be invoked by explicit commands. With our system, the user sees isodose contours being updated automatically and continuously as the plan is edited; this greatly facilitates plan optimization. The complexity of parallel processing has resulted in a 'conventional wisdom' which discourages this technique. The usual approach is to have parallel processes share a common global data structure, which makes interaction hard to control and discourages modularity and data abstraction. We have developed an alternative approach based on message streams which instead enhances modularity and data abstraction while still providing the advantages of parallel processing. The system is very reliable and is used routinely in a practical clinical environment.

Computer Simulation↗
PubMed1993

The major merozoite surface protein as a malaria vaccine target.

Experts gathered for two days in the summer of 1992 at the National Institutes of Health and the Walter Reed Army Institute of Research to discuss the potential of a major merozoite surface protein (MSP-1) in malaria vaccine development. The participants came in an exemplary spirit of co-operation, sharing ideas and unpublished data toward the common goal of a malaria vaccine. Their conclusions are presented here by Carter Diggs, Ripley Bollou and Lou Miller.

Journal Article↗
PubMed1986

Operating room surveillance: a new approach in reducing hip and knee prosthetic wound infections.

A prospective study of surgical wound infections (SWI) in hip prosthesis surgery and total hip and knee replacements at two community hospitals with common surgical staffs was begun in May 1982. The rates of SWI during the first 7 months for four orthopedic surgeons were 9% (3/32) for hip prosthesis surgery and 16.7% (3/18) for total hip and knee replacement, with 12% (6/50) overall. To reduce infections, each orthopedic surgeon agreed to intraoperative surveillance (IOS) of two procedures (hip prosthesis or total hip or knee replacement) by the infection control nurse at each hospital. Significant IOS findings were too many persons in the operating room (five to nine persons), operating room doors opened frequently (25 to 50 times), inconsistent use of prophylactic antibiotics, and excessive conversation. In January 1984, IOS data and recommendations were shared with each orthopedic surgeon, the operating room staff, and the anesthesia personnel. Subsequently, a statistically significant drop in SWI was realized for total hip and knee replacement (1/36 versus 5/36, p = 0.05) and overall (3/73 versus 14/116, p = 0.05). The drop in SWI for hip prosthesis surgery was not statistically significant (2/37 versus 9/80, p greater than 0.10). IOS and individualized communication were effective in reducing SWI.

Aged↗
PubMed1994

The effects of azapirones on serotonin1A neurons of the dorsal raphe.

1. The effects of buspirone, gepirone, ipsapirone and tandospirone on spontaneously discharging serotonergic neurons of the dorsal raphe were determined under the same experimental conditions. 2. Buspirone, gepirone, ipsapirone and tandospirone were equally efficacious and acted in a dose-dependent manner to totally inhibit the spontaneous activity of serotonergic neurons. 3. Based on their effects six min after administration (i.p.), their ED50 values were: buspirone, 134 micrograms/kg; ipsapirone, 220 micrograms/kg; gepirone, 225 micrograms/kg; tandospirone, 198 micrograms/kg. 4. The similarity of these ED50 data suggest that they share a similar chemical structure that binds to the 5-HT1A receptor, most likely it is "N-C-C-C-C-N" aliphatic backbone. 5. Buspirone and tandospirone required 4 or more min to totally block the spontaneous activity, while gepirone and ipsapirone blocked it in 3 min. 6. The dose-response curves from buspirone and tandospirone demonstrated enough dissimilarity to the dose-response curves from gepirone and ipsapirone to suggest differences in their rates of absorption, and/or differences in the production of active and inactive metabolites.

Animals↗
PubMed2006

Proteomic analysis of rat hippocampus and frontal cortex after chronic treatment with fluoxetine or putative novel antidepressants: CRF1 and NK1 receptor antagonists.

Chronic administration of antidepressants is required for their efficacy, suggesting the involvement of long-term modifications. As the impact of antidepressant treatment on the brain molecular machinery is not completely understood, we performed a proteomic analysis of rat hippocampus and frontal cortex after chronic treatment with fluoxetine, with an NK1 receptor antagonist, GR205171, and a CRF receptor 1 antagonist, DMP696. After 2D electrophoresis, protein expression levels were compared with both univariate and multivariate statistical analyses and identified by mass spectrometry. All treatments modified levels of actin isoforms, whereas both fluoxetine and GR205171 reduced synapsin II. Fluoxetine treatment increased ERK2 and NP25 and decreased vacuolar ATP synthase. After GR205171 treatment, protein disulphide isomerase A was reduced; dynamin 1 and aldose reductase increased. DMP696 modulated DRP2, pyruvate kinase, LDH and ATP synthase. Although each compound induced a specific pattern of protein modulation, data suggest that antidepressants share the ability of modulating neural plasticity.

Animals↗
PubMed2006

The effect of misclassification errors on case mix measurement.

Case mix systems have been implemented for hospital reimbursement and performance measurement across Europe and North America. Case mix categorizes patients into discrete groups based on clinical information obtained from patient charts in an attempt to identify clinical or cost difference amongst these groups. The diagnosis related group (DRG) case mix system is the most common methodology, with variants adopted in many countries. External validation studies of coding quality have confirmed that widespread variability exists between originally recorded diagnoses and re-abstracted clinical information. DRG assignment errors in hospitals that share patient level cost data for the purpose of establishing cost weights affects cost weight accuracy. The purpose of this study is to estimate bias in cost weights due to measurement error of reported clinical information. DRG assignment error rates are simulated based on recent clinical re-abstraction study results. Our simulation study estimates that 47% of cost weights representing the least severe cases are over weight by 10%, while 32% of cost weights representing the most severe cases are under weight by 10%. Applying the simulated weights to a cross-section of hospitals, we find that teaching hospitals tend to be under weight. Since inaccurate cost weights challenges the ability of case mix systems to accurately reflect patient mix and may lead to potential distortions in hospital funding, bias in hospital case mix measurement highlights the role clinical data quality plays in hospital funding in countries that use DRG-type case mix systems. Quality of clinical information should be carefully considered from hospitals that contribute financial data for establishing cost weights.

Diagnosis-Related Groups↗
PubMed2007

Severe asthma: lessons from the Severe Asthma Research Program.

Severe asthma affects only a small percentage of the asthma population. However, these patients remain poorly understood and difficult to treat. Because the numbers are relatively small (10% or less of the asthma population), a network approach with shared protocols, samples, and data provides a unique opportunity to recruit the numbers of subjects necessary to perform adequately powered studies. The Severe Asthma Network (Severe Asthma Research Program) was established by the National Heart, Lung, and Blood Institute in 2001 to advance collectively the study of severe asthma to determine factors that differentiated these patients or subjects from those with milder asthma. Nearly 800 subjects have been recruited in less than 4 years to begin to address these differences. Future studies will specifically evaluate the role of inflammatory/oxidative processes, infection, genetics, and the distal lung in the pathogenesis of severe asthma.

Asthma↗
PubMed2005

Clinical utility of the Food and Drug Administration Electrocardiogram Warehouse: a paradigm for the critical pathway initiative.

Although there are rising public expectations about the prospects for new therapies based on advances in biomedical discoveries, the rate of new product submissions to the Food and Drug Administration (FDA) has not been increasing. Alarmingly, over the past 6 years, there has been a 30% decline in submissions. The reasons for this are multifactorial and include new science not at its full potential, mergers/business arrangements have decreased candidates, chronic disease is harder to study, the failure rate has not improved, and rapidly escalating costs and complexity. Notably, societal investment in research and development to improve the drug approval process has been lacking in contrast to the large investments, both private and public, in basic research and specific product advances. The Critical Path Initiative has been developed by the FDA to combat many of these issues. This initiative is designed to be collaborative between government, academic, industry, and patient groups. The partnership is designed to expand product opportunities by sharing existing knowledge and data, allowing the development of enabling standards, to improve drug development and approval. A central tenant of Critical Path is a focus on the evaluative science of the drug approval process, including both efficacy and safety measures. The FDA Electrocardiogram Warehouse is 1 example where a government resource could be used by a confluence of groups to improve the science surrounding important components of the drug approval process such as cardiac safety evaluation.

Critical Pathways↗
PubMed2006

Differential effects of cannabis extracts and pure plant cannabinoids on hippocampal neurones and glia.

We have shown previously that the plant cannabinoid cannabidiol (CBD) elevates intracellular calcium levels in both cultured hippocampal neurones and glia. Here, we investigated whether the main psychotropic constituent of cannabis, Delta(9)-tetrahydrocannabinol (THC) alone or in combination with other cannabis constituents can cause similar responses, and whether THC affects the responses induced by CBD. Our experiments were performed with 1 microM pure THC (pTHC), with 1 microM pure CBD (pCBD), with a high-THC, low CBD cannabis extract (eTHC), with a high-CBD, low THC cannabis extract (eCBD), with a mixture of eTHC and eCBD (THC:CBD=1:1) or with corresponding 'mock extracts' that contained only pTHC and pCBD mixed in the same proportion as in eTHC, eCBD or the 1:1 mixture of eTHC and eCBD. We detected significant differences in neurones both between the effects of pTHC and eTHC and between the effects of pCBD and eCBD. There were also differences between the Ca(2+) responses evoked in both neurones and glia by eTHC and mock eTHC, but not between eCBD and mock eCBD. A particularly striking observation was the much increased response size and maximal responder rates induced by the mixture of eTHC and eCBD than by the corresponding 1:1 mixture of pTHC and pCBD. Our data suggest that THC shares the ability of CBD to elevate Ca(2+) levels in neurones and glia, that THC and CBD interact synergistically and that the cannabis extracts have other constituents yet to be identified that can significantly modulate the ability of THC and CBD to raise Ca(2+) levels.

Animals↗
PubMed2026

From complexity to clarity: Building dashboards for hit selection in high throughput screens.

High throughput screening produces large, complex datasets that are difficult to interrogate without programming expertise, making hit selection time-consuming and inflexible. While instrument software and commercial tools offer partial solutions, they often lack adaptability or require costly infrastructure. Interactive dashboards provide an effective alternative by enabling dynamic filtering and integrated visualization within a single interface. Here, we present simple R Markdown-based templates for creating customizable, modular dashboards for screen data analysis. Built using the flexdashboard and crosstalk R packages, and HTML widgets, these lightweight, easy-to-build HTML dashboards require no complex installation process or installation of licensed software. They support linked visualizations, threshold-based filtering (e.g., Z-score, p-value, fold change), and interactive data exploration and are shared as a standalone HTML file. This framework enables rapid, flexible hit selection across diverse high throughput screening applications and is designed for users with basic R experience.

High-Throughput Screening Assays↗
PubMed2003

Zea mays ontology--a database of international terms.

Data retrieval, comprehension and sharing within and between plant-based databases are essential to exploit comparative genomic information to elucidate functional aspects of plant biology and to conduct studies of synteny and homology. However, the functionality is often hampered by the variability of terms used to describe comparable objects. The Zea mays Plant Structure Ontology database is designed to overcome this problem via the provision of a controlled vocabulary that facilitates knowledge sharing. It comprises international botanical terms, references, synonyms, and phylogenetic information and is open-source.

Databases, Factual↗
PubMed2002

Relationship of bursal anti-steroidogenic peptide (BASP) and histone H1.

Previous in vitro research from our laboratory has demonstrated the existence of a protein purified from the chicken bursa of Fabricius, with potent antisteroidogenic and antiproliferative action on granulose cells and lymphocytes, respectively called Bursal anti-steroidogenic peptide (BASP). This protein is heat-labile, basic, and amino- and carboxy-terminus blocked. In highly purified form, the protein presents as a doublet on SDS-PAGE electrophoresis with an apparent MW of approximately 29 and approximately 32 kDa. Recently, Nanoflow Q-TOF Mass Spectrometry amino acid sequencing allowed determination of a convincing partial amino acid sequence, strongly suggesting a probable relationship of BASP with histone H1. Bursal cDNA expression library screening, using an antibody produced against BASP, also identified a clone with a sequence matching histone H1. Presently, we have demonstrated that SDS-PAGE electrophoresis of highly purified and bioactive BASP, and commercially-available calf thymus derived histone H1, produced similar doublets at approximately the same apparent MW, and that the electrophoretic profile of these 2 preparations were strikingly similar following 2 dimensional gel electrophoresis. The BASP doublet produced on SDS-PAGE was recognized by a commercially available monoclonal antibody recognizing a highly conserved region of histone H1. Furthermore, calf thymus histone H1 was found to suppress mitogen-stimulated chicken B-cell proliferation in a concentration-related manner, similar to the action of BASP. These data indicate that BASP shares substantial structural homology with, and may be identical to, histone H1.

Animals↗