Spheres of influence: no POPS. Persistent organic pollutants.
Explore the source record for details and available documents.
Environmental Pollution↗
Biomedical subjects
C W Schmidt
Publications and source records attributed to C W Schmidt.
Poisoning young minds.
For some neurotoxic chemicals, neurobehavioral effects are now considered to be among the most sensitive end points yet detected, particularly if exposures occur during critical windows of vulnerability. Chemically induced problems with perception and cognitive ability in children can be hard to identify; teasing them out of a host of genetic and sociocultural influences is a difficult task. Today, most data on environmentally relevant neurobehavioral effects in children are concentrated in three chemicals: lead, methylmercury, and polychlorinated biphenyls. But mounting evidence of the neurobehavioral effects of chemicals along with growing public concern over pediatric mental health problems such as attention deficit/hyperactivity disorder dictates that scientists and legislators improve test methods, explore mechanisms, and develop appropriate strategies for risk assessment and policy making.
Child↗
Chloroform: An EPA test case.
In March 1998, the U.S. Environmental Protection Agency (EPA) published a proposal to raise the drinking water maximum contaminant level goal (MCLG) for chloroform, a suspected human carcinogen, from zero to 300 parts per billion. The proposal marked a departure from the agency's traditional reliance on linear dose-response models in performing risk assessment, and reflected the new thinking contained in the 1996 draft update to the agency's cancer risk assessment guidelines. The updated guidelines emphasize mechanisms of action and descriptions of the conditions under which carcinogenic hazards are likely to be expressed.
Animals↗
Trading trash: why the U.S. won't sign on to the Basel convention.
Environmentalists worry that hazardous wastes produced in industrialized nations are being dumped in cash-starved developing countries--the countries with the least political or economic clout to resist and the fewest resources for managing these toxic imports. Imported waste can pose a serious threat to the health of human populations and ecosystems if not managed appropriately. In 1989, the international community initiated efforts to reduce the flow of hazardous wastes from industrialized countries to developing countries by drafting a treaty known as the Basel Convention on the Control of Transboundary Wastes and their Disposal. The convention's mission is to strictly regulate the international transfer of hazardous wastes and to ensure that wastes are managed and disposed of in an environmentally sound manner. Although the United States supports the convention in theory, it remains the only industrialized country within the Organization for Economic Cooperation and Development yet to ratify it. However, legislation drafted by the Clinton administration that is soon to go before the 106th Congress could make the United States a party to the convention.
Developing Countries↗
Answering the endocrine test questions.
Evidence suggesting that certain chemicals may bind to endogenous hormone receptors and disturb normal endocrine functioning, thereby increasing the risk of reproductive problems and cancer in humans, has led to international efforts to screen chemicals for endocrine activity and potential health effects. The U.S. Environmental Protection Agency (EPA) has recommended that some 87,000 commercial chemicals for which there currently are inadequate toxicity data be evaluated. In December 1998, the EPA's Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) recommended the use of a tiered system of screening and testing assays to sequentially eliminate chemicals for which further testing is deemed unnecessary. The first step toward implementing such a system-validation of the tests to be used-is presenting some challenges, however, with stakeholders disagreeing over which tests to validate, how extensively to validate them, and how much it will cost.
Animals↗
Caught in the middle: should the World Trade Organization settle environmental disputes?
Since its inception in 1995, the World Trade Organization (WTO) has arbitrated trade disputes between its members in part by deciding whether unilateral actions by its 134 member nations such as trade bans or restrictions violate international free trade rules and authorizing penalties against members that are found to be noncompliant with such rules. The WTO is criticized by those who believe its emphasis on free trade undermines national environmental and public health protection efforts. Recent disputes over the importation of hormone-treated beef and genetically modified crops have focused attention on how the WTO arbitrates disputes having environmental and public health implications and sparked criticisms as to whether the organization is qualified to do so.
Commerce↗
A functional link for major TCR expansions in healthy adults caused by persistent Epstein-Barr virus infection.
Dramatic clonal expansions of unknown functional significance have been documented in the T cell receptor (TCR) alpha beta peripheral blood repertoires of apparently healthy adults. In this study, we provide evidence that persistent infection with the ubiquitous Epstein-Barr virus (EBV) causes major distortions within the memory repertoire of healthy virus carriers. Using complementarity determining region 3 (CDR3) length analysis to measure repertoire diversity, dominant expansions that dramatically skewed the entire TCRBV6 blood repertoire towards oligoclonality were enriched in the CD8(+)CD45RO+CD45RA- subset of HLA B8(+) healthy virus carriers. Evidence of phenotypic heterogeneity between individuals was also observed for these expansions based on their variable coexpression of CD45RO and CD45RA. TCR junctional region sequencing revealed that these expansions were clonal and that they represented commonly selected HLA B8-restricted memory cytotoxic T cells that recognize the immunodominant latent EBV epitope, FLRGRAYGL. Furthermore, the functional identity of these virus-specific CD8(+) T cells was confirmed by their FLRGRAYGL-specific cytotoxicity. Therefore, the functional significance of dramatic clonal expansions in healthy adults can be linked in some cases to virus-specific CD8(+) T cells that play an essential role in immunosurveillance. This first identified link for expansions in the circulation of healthy adults strongly implies that restricted-memory TCR responses to environmental antigens play a pivotal role in expansion development, which should have an important impact on studies interpreting TCR expansion patterns in health and disease.
Adult↗
The labyrinthine ways of cancer immunotherapy--T cell, tumor cell encounter: "how do I lose thee? Let me count the ways".
Explore the source record for details and available documents.
Antigen-Antibody Reactions↗
Childhood cancer: A growing problem.
Childhood cancer is the leading cause of disease-related death among children in the United States,and rates are increasing by approximately 1% each year. Unfortunately,the science of epidemiology has not provided definitive answers to the question of why cancer strikes children.
Child↗
Natural born killers.
This year, 30 million acres of the corn, cotton, and potatoes planted in the United States will have been genetically engineered to produce an endotoxin normally found in the microbe Bacillus thuringiensis (Bt), a self-contained pesticide that will be toxic only to target insects. Transgenic pest-resistant crops are a cost-effective alternative to chemical pesticides, and may offer a way to help feed the world's growing population with minimal environmental impact.
Fruit↗
Psychiatric and substance use comorbidity among treatment-seeking opioid abusers.
BACKGROUND: Major studies of psychiatric comorbidity in opioid abusers reported rates of comorbidity that far exceeded general population estimates. These studies were published more than a decade ago and reported on few women and few substance use diagnoses. METHODS: Psychiatric and substance use comorbidity was assessed in 716 opioid abusers seeking methadone maintenance. Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition diagnostic assessment was conducted 1 month after admission. Rates of psychiatric and substance use disorder were compared by gender, and associations were assessed between psychiatric comorbidity and dimensional indexes of substance use severity, psychosocial impairment, and personality traits. RESULTS: Psychiatric comorbidity was documented in 47% of the sample (47% women and 48% men). Antisocial personality disorder (25.1%) and major depression (15.8%) were the most common diagnoses. Patients had at least 2 substance use diagnoses, most often opioid and cocaine dependence. Demographics, substance use history, and personality variables discriminated between patients with vs without comorbidity. Psychiatric comorbidity also was associated with a more severe substance use disorder. CONCLUSIONS: Psychiatric comorbidity, especially personality and mood disorder, was common in men and women. The positive associations between psychiatric comorbidity and severity of substance use and other psychosocial problems were most consistent among those with antisocial personality.
Adolescent↗
A case report: immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy.
The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient, with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophila. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases: however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.
Autopsy↗
Immunotherapy, including gene therapy, for metastatic melanoma.
Current standard therapy for distant metastatic melanoma is ineffective and often compromises the quality of a patient's life. Immunotherapy is briefly reviewed in relation to its many forms: from local non-specific to the more recent specific vaccines, including those using specific melanoma peptides (e.g. from the proteins encoded by melanoma-associated gene (MAGE)) and those involving genetically transduced autologous melanoma cells using retroviral vectors in vitro. The mode of action of genetically transduced melanoma cells incorporating the granulocyte macrophage colony stimulating factor (GM-CSF) gene (GVAX) is presented as a paradigm for cytokine-mediated strategies. Trials of GVAX and other cytokine gene strategies are under way in Brisbane, Boston and Amsterdam, and some interim perspectives on the clinical outcomes and immunological mechanisms involved are sketched. Some of the compounding problems in immunotherapeutic strategies for cancer are identified, and possible adjunct manoeuvres for overcoming them are discussed.
Antigens, Neoplasm↗
25 years--a look back.
Explore the source record for details and available documents.
History, 20th Century↗