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N H Adams

Publications and source records attributed to N H Adams.

8 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↗