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N H Adams

Publications and source records attributed to N H Adams.

11 recordsLinked to original sources
PubMed1996

Induction of CYP1A1 and ALDH-3 in lymphoid tissues from Fisher 344 rats exposed to 2,3,7,8-tetrachlorodibenzodioxin (TCDD).

The immune system is a primary target for toxic insult by a number of drugs and environmental chemicals, many of which require activation to toxic metabolites by drug-metabolizing enzymes. We compared the induction of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1A1) and aldehyde dehydrogenase (ALDH), in lymphoid tissues of F344 rats following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). ALDH was induced in both the spleen and the thymus after TCDD treatment, with maximal expression at 9 and 15 days, respectively. Thymic microsomal preparations from TCDD-treated animals expressed elevated levels of inducible CYP1A1 as compared to microsomes from the spleens of treated animals or tissues from control rats. TCDD treatment also resulted in increased ethoxyresorufin-O-deethylase (EROD) activity in the thymus. There were no detectable mRNA transcripts for CYP1A1 in peripheral blood or splenic lymphocytes from treated animals; however, CYP1A1 transcripts were induced in isolated thymocytes, whole spleen, and whole thymus. In vitro exposure to TCDD did not result in induction of immunoreactive CYP1A1 in thymocytes unless simultaneously activated with the mitogen, phytohemagglutinin (PHA). Immunohistochemical localization of CYP1A1 in immune tissues indicated that cells other than the lymphoid populations are responsible for the increased CYP1A1 expression. The pattern of CYP1A1 induction was related to the expression of the Ah receptor (AhR) in immune tissues. Western blot analyses demonstrated less AhR present in peripheral blood lymphoid cells and spleen, as compared to whole tissues. These studies indicate that while drug-metabolizing enzymes are present in immune tissues, the induction of enzymes is selective in different lymphoid cells.

Aldehyde Dehydrogenase↗
PubMed1995

Comparative assessment of metabolic enzyme levels in macrophage populations of the F344 rat.

The immune system is a direct target for toxic insult by a number of drugs and other chemicals, many of which require activation to toxic metabolites by drug-metabolizing enzymes. We compared the induction of drug-metabolizing enzymes, including cytochrome P450 1A1 (CYP1A1) and aldehyde dehydrogenase (ALDH), which are differentially expressed in various macrophage populations following treatment of F344 rats with the inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Kupffer cells, alveolar macrophages and splenic macrophages from TCDD-treated animals expressed elevated levels of inducible CYP1A1 as compared to other macrophage subpopulations or cells from control rats. TCDD treatment also resulted in increased ethoxyresorufin-O-deethylase (EROD) activity and total cytochrome P450 content in tissue-derived macrophages. Immunoreactive protein and mRNA transcripts for CYP1A1 were not detectable in resident peritoneal macrophages or peripheral blood monocytes. Examination of aromatic hydrocarbon receptor (AhR) levels in macrophage populations suggests that the ability of TCDD to induce metabolic enzymes in specific cell types correlates well with AhR expression. In vivo activation of macrophages, using either Bacillus of Calmette and Guérin, Mycobacterium tuberculosis (BCG) or polyinosinic:polycytidylic acid (Poly I:C), caused no significant alteration in the levels of induction of CYP1A1. ALDH-3 induction was similar in all macrophage populations examined. These studies indicate that macrophages, particularly those from portals of entry, may be induced to produce increased levels of specific enzymes, and the induction is dependent upon their maturational stage rather than their activation state. The metabolism of xenobiotics to toxic intermediates by immune cells and its role in immunosuppression are discussed.

Aldehyde Dehydrogenase↗
PubMed1993

Regulation of cytochrome P-450 isozymes by methylenedioxyphenyl compounds.

Regulation of cytochrome P-450 isozymes 1a-1, 1a-2, and 2b-10 by methylenedioxyphenyl compounds was studied by measuring levels of mRNA, protein, and enzyme activity in hepatic tissue from C57BL/6 (Ah+) and DBA/2 (Ah-) mice dosed with isosafrole (ISO) or piperonyl butoxide (PBO). Increases in 1a-2 and 2b-10 protein were observed for ISO and PBO in both strains of mice, suggesting an Ah receptor-independent mechanism for induction of these isozymes; 1a-1 induction, however, was seen only in C57 mice. Piperonyl butoxide was the more potent inducing agent in both strains. In C57 mice treated with five dose levels of PBO, induction of 1a-1 mRNA, protein, and enzyme activity were seen at doses equal to or greater than 104 mg/kg, but were not detected at lower doses. With isosafrole, induction of 1a-1 mRNA was observed only at the highest dose tested (400 mg/kg); however, neither 1a-1 protein nor increased enzymatic activity was seen at this dose. Dose-response studies showed maximum inducible levels for 1a-2 and 2b-10 protein, beyond which the mRNAs continued to increase while the protein levels remained constant.

Animals↗
PubMed1991

Attitudes of psychiatric patients and their relatives to involuntary treatment.

In 1979 a Guardianship Board assumed responsibility in South Australia for the welfare of those mentally ill or handicapped people unable to look after their own health or safety, or to manage their own affairs. This study examines the attitudes to guardianship and involuntary treatment of 79 patients referred to the Board from a psychiatric hospital, all of whom were under guardianship at the time of the study. Forty-seven of their relatives took part in the project, which included measures of patients' psychiatric symptoms and relatives' punitiveness. Although almost 70% of patients objected to Guardianship in principle, they made more positive than negative statements about it. Nearly 60% rated involuntary treatment, including medication, as helpful. Patients reported a level of psychiatric symptoms less than half of that of a psychiatric outpatient sample. Relatives were strongly in favour of Guardianship, stating frequently that it allowed an improved relationship between themselves and the patient. Patients who believed that they were suffering from a mental illness were comparatively happy about being under Guardianship, and a belief that the patient was mentally ill was significantly associated with reduced extrapunitiveness in relatives.

Activities of Daily Living↗
PubMed1987

An interlaboratory study of an EPA/Ames/Salmonella test protocol.

7 laboratories participated in a collaborative study to evaluate an EPA standard protocol for the Ames test. The study utilized Salmonella typhimurium (strains TA98 and TA100) and 3 metabolic activation levels (0%, 2%, and 10% S9 in the S9 mix). 6 pure chemicals and 2 complex mixtures were tested as coded unknowns. Ability to obtain qualitative results in agreement with published data was less (% agreement) than that reported in an earlier study (% agreement) by de Serres and Ashby (1981) in which each laboratory used its own protocol. The conclusion from analysis of the quantitative data from this interlaboratory Ames study was that both intralaboratory and interlaboratory variations were substantial. Results for the same substance varied by an order of magnitude or more (CV of 115%) when the mutagenic response was measured as the slope of the dose response in revertants/microgram. Taking interlaboratory variation into account, one chemical must be more than an order of magnitude more mutagenic than another (ratio of slopes greater than 10) to have only an even chance of finding a statistically significant difference between the two chemicals at the 5% level. Such large variations must be taken into account when evaluating Ames/Salmonella data.

Analysis of Variance↗
PubMed1983

Deinstitutionalization: the data demythologized.

Many past studies of data on deinstitutionalization have used an overly simplistic and often misleading approach, which has led to a number of "myths" of deinstitutionalization. The authors present data on the changing mental health service system collected by the Division of Biometry and Epidemiology of the National Institute of Mental Health, and they analyze the data to reveal trends that disprove a number of the commonly accepted myths. Through their analysis they show that outpatient care has not replaced inpatient care, that public institutions, particularly state mental hospitals, have not been replaced by community-based facilities, and that private resources have not replaced public ones as the bearer of the cost of caring for the mentally ill. They conclude that the availability and quality of mental health services and the effect of these services on patients and their communities are difficult issues for future research.

Community Mental Health Services↗
PubMedDate not supplied

Quality assurance reviews: how they differ from peer reviews.

Research papers and reports written by scientists and engineers in the United States Environmental Protection Agency are reviewed by the agency's quality assurance staff. EPA papers and reports are subjected to peer reviews that check for the validity of conclusions and the general agreement with the body of technical knowledge in the subject area. Quality assurance reviews differ from peer reviews in that the focus of the quality assurance review is on the following criteria: Consistency: Were reasonable and consistent units of measurement and generally acceptable formulas used throughout? Are the appropriate number of significant figures reported? Correctness: Were matrix-compatible methods used? Were measurements within the working range of the method? Can measurements be traced to a recognized standard or source (e.g., the National Institute of Standards and Technology)? Can calculations be verified, starting from representative raw data and proceeding to the summary data presented in the paper or report? Coherence: Do the stated conclusions follow from the data presented? Are the assumptions clearly stated? Are inconsistencies between data and conclusions discussed? Clarity: Are special terms and acronyms defined? Can a person with a general technical background in the subject understand the paper or report? Conformance: Did the study follow the test/quality assurance plan, with appropriate calibrations and other quality-control checks, audits, and data validations? If not, is there a discussion of problems? Concordance: Were data quality objectives met? Were the data quality indicator goals achieved for precision, accuracy, representativeness, comparability, and completeness? The importance of these quality assurance review criteria are discussed along with examples from current work.

Authorship↗
PubMedDate not supplied

Never audit alone--the case for audit teams.

UNLABELLED: On-site audits, conducted by technical and quality assurance (QA) experts at the data-gathering location, are the core of an effective QA program. However, inadequate resources for such audits are the bane of a QA program and, frequently, the proposed solution is to send only one auditor to the study site. There are several reasons why audits should be performed by more than one person: 1. SAFETY: Audits of EPA projects frequently involve hazardous chemicals or other environmental hazards. They also often involve working after normal work hours in remote locations with dangerous equipment. It is unsafe to work alone under such conditions. 2. Skills: Many of EPA's projects are multidisciplinary, involving multiple measurements systems, several environmental media, and complex automated data collection and analysis systems. It is unlikely that one auditor would have the requisite skills to assess all of these operations. 3. Separateness: Two auditors can provide two (sometimes differing) perspectives on problems encountered during an audit. Two auditors can provide complementary expertise and work experience. Two auditors can provide twice the surveillance power. 4. Support: The operations that need to be assessed are sometimes in different parts of a site, requiring two auditing devices or considerable commuting time. Also, auditors are occasionally diverted by managers wishing to show their best efforts rather than the whole operation; if two auditors are on-site, one can interview managers while the other talks with technical staff. If there is a dispute, one auditor can support the other in verifying observations. 5. Savings: Although sending one auditor is perceived to be a cost-saving measure, it may be more economical to send two auditors. Time on site (lodging, food) is decreased, more of the project is assessed in one visit, less pre-audit training is required, and report preparation is accelerated. In summary, sending more than one auditor on a field audit is smarter, safer and more effective, and can be less expensive in the long run.

Environmental Health↗
PubMedDate not supplied

The use of method detection limits in environmental measurements.

Environmental measurements often produce values below the method detection limit (MDL). Because low or zero values may be used in determining compliance with regulatory limits, in determining emission factors (typical concentrations emitted by a given type of source), or in modeling efforts, there is considerable interest in methods for determining detection limits and in procedures for using MDLs in summary statistics. Selection of methods for determining detection limits and treatment of MDL data should depend on the end-use of the data. The MDL should be determined in the environmental matrix that contains the analyte of interest. Treatment of missing values (values below the MDL) should be specified before the initiation of a measurement effort. When calculating a mean value for a source or area, one approach is to set the missing values at the MDL. This approach is appropriate when there are significant risks associated with incorrectly assuming a low level of a toxic compound; this method of summarizing data introduces a positive bias. Missing values may be assumed to equal zero if there is not a high risk of overlooking a hazard; this method produces a negative bias. However, if enough measurement data are available and the distribution of these data can be established then look-up tables can be used to estimate missing values, using statistically based estimates, without introducing high or low biases in a calculated mean.

Environmental Monitoring↗