Reaction of cytochrome P450 enzymes with arylacetylenes results in heme N-alkylation [e.g., Komives, E. A., and Ortiz de Montellano, P. R., (1985) J. Biol. Chem. 260, 3330-3336] and/or protein modification [e.g., Gan, L.-S. L., Acebo, A. L. and Alworth, W. L. (1984) Biochemistry 23, 3827-3836]. To clarify the factors that determine whether heme or protein alkylation occurs, we have investigated the cytochrome P450 1A1-catalyzed oxidation of 1-ethynylpyrene (1-EP) and phenylacetylene (PA). Cytochrome P450 1A1 in microsomes from beta-naphthoflavone-induced rats is inactivated in a time- and NADPH-dependent manner by 1-EP and PA. Parallel loss of the heme chromophore is observed with PA but not with 1-EP, although partial heme chromophore loss is observed when the purified, reconstituted enzyme is inactivated by either agent. Product analysis shows that 1-EP and PA are oxidized to, respectively, (1'-pyrenyl)-acetic and phenylacetic acids. In contrast to the inactivation of cytochrome P450 2B1 by PA, no isotope effect is observed on enzyme inactivation or metabolite formation when the acetylenic hydrogen is replaced by deuterium in either 1-EP or PA. Inactivation of cytochrome P450 1A1 by 1-EP results in covalent binding of 0.8-0.9 equiv (relative to total cytochrome P450 content) of the inhibitor to the microsomal protein. The results demonstrate that a single isozyme can be inactivated, depending on the structure of the arylacetylene, by heme or protein alkylation. Spectroscopic binding constants (Ks) show that 1-EP binds to the enzyme with > 2000 times greater affinity that PA.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study was to investigate whether imprint cytology can improve the diagnostic accuracy of computed tomography-guided transthoracic core biopsy.Between October 1997 and June 2004, thoracic lesions in 622 patients underwent biopsy using 19-gauge coaxial guiding needles and 20-gauge biopsy needles under computed tomography guidance. Touch imprint cytology and histopathology were performed for all biopsy specimens.Of these lesions, 431 (74.1%) were diagnosed as malignant, 151 (25.9%) as benign and 40 (6%) as nondiagnostic. Imprint cytology plus histology shows an improved diagnostic accuracy of 96.4% compared with that of imprint cytology alone (92.3%) or histopathology alone (93.0%). Procedure-related complications requiring further treatment occurred in eight (1.4%) patients.In conclusion, imprint cytology combined with histopathology can improve the diagnostic accuracy of computed tomography-guided transthoracic needle biopsy.KEYWORDS: Computed tomography, cytology, diagnostic accuracy, needle lung biopsy P ercutaneous transthoracic needle biopsy (TNB) is an important diagnostic tool in the management of lung and mediastinal lesions [1][2][3][4][5]. Fine-needle aspiration (FNA) with computed tomography (CT) guidance has an accuracy and sensitivity of 76-95% for the detection of malignancy in solitary lung nodules [3][4][5]. Automated biopsy needles can acquire more core specimens and increase the diagnostic sensitivity to 84-96% [6,7]. Coaxially guided needle biopsy minimises the risk associated with repeated pleural penetration and increases the volume of tissue retrieved compared with aspiration cytology or single-shot core biopsy. The diagnostic sensitivity for malignancy is 77-96% and the specificity for benign disease is 91-94% with automated coaxial core biopsy [1,2,8].Efforts to increase the diagnostic accuracy of image-guided TNB include frozen-section pathology [9] or FNA cytology combined with core biopsy under CT fluoroscopic guidance [10]. Touch imprint cytology is useful for diagnosing metastasis in surgically removed lymph nodes in breast cancer and better than conventional haematoxylin-eosin staining of paraffin sections [11,12]. However, data regarding imprint cytology and TNB are very limited. Recently, PAULOSE et al. [13] showed that imprint cytology could assist rapid diagnosis of lung cancer metastasis in mediastinal lymph nodes following CT-guided TNB. LIAO et al. [14] demonstrated improved diagnostic accuracy by using imprint cytology following ultrasound (US)-guided TNB of peripheral lung lesions. The role of touch imprint cytology in CT-guided coaxial core biopsy of intrathoracic lesions has not been investigated. The objective of the present study was to evaluate whether touch imprint cytology as an adjunct to CT-guided coaxial core biopsy can improve diagnostic accuracy for thoracic lesions. METHODS AND MATERIALS Study subjectsTissue specimens from 622 patients who underwent CT-guided TNB of thoracic lesions between October 1997 and June 2004 at the Natio...

Data are limited regarding risk factors for mortality among patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) in areas with low HIV prevalence and intermediate TB burden, such as the Western Pacific region. This study aimed to assess such risk factors in Hong Kong, which has an intermediate TB burden and low HIV prevalence. Methods: We conducted a retrospective cohort analysis of adult patients reported to the Hong Kong TB-HIV Registry between 2006 and 2015. Baseline characteristics were compared with Kaplan-Meier estimates. Cox proportional hazards regression modelling was used to identify factors associated with mortality. Results: Of 299 patients studied, 21 (7.0%) died within 12 months of anti-TB treatment (median [interquartile range], 7.5 [3.8-10] months). The median age of death was 54 (interquartile range, 40.5-75.0) years. The cause of death was TB in five and unrelated to TB in the remaining 16. Cox proportional hazards regression showed that older age (adjusted hazard ratio=4.5; 95% confidence interval [CI]=1.4-14.9), history of drug addiction (4.6; 95% CI=1.6-13.0), and low baseline CD4 cell count of <50/µL (2.9; 95% CI=1.1-7.7) were independent risk factors for death within 12 months.

Objective To evaluate whether a policy to treat latent tuberculosis identified by annual tuberculin sensitivity testing is effective for tuberculosis control in human immunodeficiency virus-infected patients in Hong Kong.Design Historical cohort study. Setting ConclusionThe established policy continues to be effective. The high risk of tuberculosis during the early period of antiretroviral therapy supports early use of tuberculin sensitivity testing. Alternatively, the strategy of universal isoniazid preventive therapy at antiretroviral therapy initiation could be studied for those with very low baseline CD4 counts.

To plug the loopholes, a specific law with heavy penalties should be adopted. This could be supplemented by non-legal measures like education of judges, lawyers, and the public; publishing the names of offending pharmacies; and emphasising the role of pharmacists to the public.