A twin study of aryl hydrocarbon hydroxylase (AHH) inducibility in cultured lymphocytes

Aryl hydrocarbon hydroxylase (AHH) inducibility was studied in cultured lymphocytes from 28 monozygotic (MZ) and 19 dizygotic (DZ) twin pairs. The results indicate that the induced level of AHH activity as well as inducibility (expressed as the ratio between levels in induced and non-induced cells) are inherited. The best (h²) estimate of heritability is 0.7. There was no suggestion that non-induced AHH activity level is an inherited trait. Inducibility of AHH was not normally distributed and the distribution observed in this limited series might even be trimodal. The results of the study appear to confirm previous reports that AHH inducibility is an inherited trait, and do not exclude the possibility that the major part of the variation is controlled by one locus.     

Aryl hydrocarbon receptor and experimental autoimmune arthritis

Aryl hydrocarbon receptor (Ahr) is thought to be a crucial factor that regulates immune responses. Many Ahr-mediated immune regulatory mechanisms have been discovered, which will likely enhance our understanding of the molecular pathogenesis of autoimmune inflammation including rheumatoid arthritis (RA). RA is a systemic inflammatory disease that affects approximately 1 % of the population and is characterized by chronic inflammation of the synovium and subsequent joint destruction. Recent findings showed that Ahr plays critical roles in the development of Th17 cells, which are key effector T cells in a variety of human autoimmune diseases including RA. Consistent with these findings, our previous study demonstrated that Ahr in T cells is important for the development of collagen-induced arthritis, a widely used murine model of human RA, possibly via the induction of Th17 cells. In addition, Ahr is an attractive molecule because tobacco smoke is a well-known environmental risk factor for RA development and Ahr agonists, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, 3-methyl cholanthrene, and benzo[a]pyrene, are major toxic components in cigarettes. This review summarizes recent findings on Ahr functions in immune cells in the context of RA pathogenesis during stimulation with smoking-derived ligands. We also discuss the potential link between Ahr and novel factors, such as microRNAs, in the development of RA, thereby providing further mechanistic insight into this autoimmune disorder.     

Mediastinoscopy in bronchogenic carcinoma

Mediastinoscopy was performed in 470 patients with bronchogenic carcinoma in the ENT Department, Aalborg. The histological diagnoses were 195 squamous cell carcinomas, 149 adenocarcinomas, and 126 anaplastic carcinomas. Metastases in the mediastinal lymph nodes were found in 177 of the 470 patients (38%). Metastatic lymph nodes were found in approximately one fifth of the squamous cell carcinomas, in almost half of the adenocarcinomas, and in about half of the anaplastic carcinomas. The need is emphasized for lymph node biopsy from both right and left tracheobronchial angles and inferior to the bifurcation irrespective of the site of the carcinoma. Contralateral metastasis was found in approximately one third of the cases, and a positive biopsy from the nodes inferior to the bifurcation was found in about 40% of the patients in whom metastasis in the mediastinum were detected. In 10% of the patients, cytological and histological examinations of specimens obtained by bronchoscopy were negative, and the diagnosis of lung cancer was made by mediastinoscopy exclusively. The value of mediastinoscopy was particularly high in the diagnosis of adenocarcinomas.     

Prevalence of aspergillosis in bronchogenic carcinoma

Bronchoalveolar lavage of 42 patients of bronchogenic carcinoma was studied to find out the prevalence of aspergillosis. Sera of the patients were also analysed for presence of anti-Aspergillus antibodies by Immunodiffusion (ID), Enzyme linked immunosorbent assay (ELISA) and dot blot assay (DBA). Aspergillus was isolated in culture from 6 (14.2%) patients of bronchogenic carcinoma. Aspergillus fumigatus was the predominant species isolated. All the strains of Aspergillus were sensitive to itraconazole, ketoconazole and amphotericin B while resistance (33.3%) was found with fluconazole. Anti-aspergillus antibodies were detected equally by ID, ELISA and DBA in 9 (21.4%) cases. The present study revealed prevalence and seroprevalance of Aspergillus in bronchogenic carcinoma to be 14.2% and 21.4% respectively. Consistent reactivity against 18 kDa Aspergillus fumigatus antigen was noted in serologically positive cases. Antibodies against 18 kDa protein antigen in western blotting may be used as a reference marker for diagnosis of aspergillosis in bronchogenic carcinoma. It is also suggested that the simplest serological technique like ID may be performed along with culture for diagnosing Aspergillosis in patients of bronchogenic carcinoma since ID, ELISA and DBA showed similar sensitivity.     

Effects of dioxin congeners on aryl hydrocarbon hydroxylase activity

In this study, we examined the effect of 1,3,6,8-tetrachlorodibenzo-p-dioxin (1,3,6,8-TCDD), octachlorodibenzo-p-dioxin (OCDD) and 2,4,6,8-tetrachlorodibenzofuran (2,4,6,8-TCDF) on aryl hydrocarbon hydroxylase (AHH) activity in cultured human lymphoblastoid cells. These compounds are considered to be no or less toxic isomers of polychlorinated dibenzo-p-dioxins (Dioxins) and polychlorinated dibenzofurans (Dibenzofurans). At a concentration of 90 ppb, 1,3,6,8-TCDD induced the enzyme activity about 2 times over the basal (untreated) AHH activity and 2,4,6,8-TCDF reduced the basal enzyme activity by about 40%. At a concentration of 5 ppb, OCDD enhanced the basal AHH activity by about 30%. In case of simultaneous treatment of 1,3,6,8-TCDD, OCDD or 2,4,6,8-TCDF with highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD), at a concentration of 7.5 ppb of each compound, the AHH activities induced by 1,3,6,8-TCDD plus 2,3,7,8-TCDD and OCDD plus 2,3,7,8-TCDD were about 25% and 43%, respectively, higher than that induced by 2,3,7,8-TCDD alone. On the contrary, at the same concentration, the enzyme activity treated with 2,4,6,8-TCDF plus 2,3,7,8-TCDD were about 30% less than that treated with 2,3,7,8-TCDD alone. It has been reported that the AHH inducibility of Dioxins and Dibenzofurans correlates well with their toxic potency. Hence, taking the results of this study into account, we should clarify the biological and/or health consequences of the mixed contamination of no or less toxic and highly toxic congeners of Dioxins and Dibenzofurans by animal experiments and epidemiological studies.     

Plasma ACTH in patients with bronchogenic carcinoma

Immunoreactive ACTH before and five hours after administration of 2 mg of dexamethasone was determined in patients examined in hospital for abnormalities on chest X-ray. Thirty patients had primary bronchial cancer, 15 had other lung conditions, mostly inflammatory infiltrations. The mean total ACTH and ACTH after dexamethasone suppression were significantly higher in the patients with bronchial cancer than in patients with other lung lesions or healthy controls. ACTH in plasma after administration of glucocorticoids was predominantly big ACTH. Several of the cancer patients had, however, ACTH levels within the same range as the other subjects. These results indicate that plasma ACTH determinations are of limited value as tumour markers for the detection of lung cancer although it is still possible that repeated sampling in patients with elevated ACTH levels may be of value when monitoring the therapy.