Metabolism of 6-chloro n-butyl phthalide in rat

6-Chloro n-butyl phthalide (CBP) was orally administered to healthy, male Wistar rats pretreated with or without 3-methylcholanthrene (3-MC) by a single dose of 150 mg/kg, and urine samples were collected for 0-24 h. The urine sample was hydrolyzed with beta-glucuronidase, extracted and concentrated for TMS derivatization, and analysed on a GC-MS system for identification of CBP metabolities. Mass spectral analysis suggests that 7 CBP metabolites were present in the urine sample, and similar metabolism patterns were viewed in rats with or without pretreatment with 3-MC. Four main metabolites of CBP in rat urine were identified as alpha-beta oxolate, beta-gamma oxolate, beta-hydroxylate and gamma-hydroxylate, based on their chromatographic and mass spectral properties. Two hydroxylates have been previously identified in CBP metabolism by rat liver microsomes. The other two metabolites with higher polarity were tentatively identified as dihydroxylation products on the n-butyl side chain by the mass spectra of their TMS derivatives. One minor metabolite was found by the isotopic effect of chlorine, but its specific structure was undetermined. The difference between in vivo and in vitro metabolic profiles of CBP is also discussed.     

Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

Premature separation of centromere and aneuploidy: an indicator of high risk in unaffected individuals from familial breast cancer families?

OBJECTIVES: Injury is the leading cause of death in the male working population of Brazil. An important fraction of these deaths are work related. Very few cohort studies of steel workers, and none from developing countries, have reported on mortality from injuries. This paper analyses mortality from work and non-work related injuries among Brazilian steel workers. METHODS: Deaths during employment from 1 January 1977 to 30 November 1992 were analysed in a cohort of 21,816 male steel workers. Mortality rates specific for age and calendar year among the workers were compared with those of the male population of the state where the plant is located. Work related injuries were analysed by comparing the mortality rates for different subgroups of the cohort. RESULTS: The number of deaths (391) was less than half that expected based on death rates of the general population. Over 60% (242) of deaths were due to injuries. Mortality from most causes was substantially below that in the general population, but that from unintentional injury, was 50% above that of the general population. Standardised mortality ratios (SMRs) were highest for the youngest and the oldest employees and for labourers and clerical workers. Mortality from motor vehicle injury was twice that expected from population rates (SMR = 209, 95% confidence interval (95% CI) 176-244). There was a 67% fall in the age adjusted mortality from occupational injuries in the study period. CONCLUSION: The healthy worker effect in this cohort was greater than that commonly found in studies of occupational groups in developed countries, probably because of a greater socioeconomic gap between employed and unemployed populations in Brazil, and unequal distribution of health care resources. Mortality was especially high for motor vehicle injuries. The fall in mortality from occupational injuries during the study period was probably due to improvement in safety standards, increased automation, and better medical care. There is a need to investigate risk factors for unintentional injuries among steel workers, especially those due to motor vehicle injuries. Prevention of occupational and nonoccupational injuries should be a main priority in Brazil.     

On measures of vulnerability of interconnection networks

With the advent of distributed and multiple processing systems, the study of interconnection networks has developed into a field of its own. In most cases, the performance measures used to characterize the reliability of such networks have been primitive.It is our purpose, in this brief paper, to survey the many available measures of the vulnerability of interconnection networks. The most widely known is classical connectivity; however, measures more recently introduced in the graph theory literature are probably a better practical metric of reliability. Our objective is to make these measures more widely known, and to spur the development of good algorithms to calculate them in practical instances.     

Exceptionally high seizure threshold: ECT device limitations

Numerous studies have confirmed the distinct biological behavior of two subsets of prostate cancer diagnosed incidentally after either transurethral resection (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH). Focal, low-grade lesions are associated with a low risk for clinical progression and are designated as stage T1a or A1. These cases have traditionally been managed conservatively with close clinical observation. In contrast, multifocal, high-volume, or high-grade tumors are associated with a more aggressive clinical course and are designated as stage T1b or A2. Early definitive intervention is usually advocated for these latter patients. Therefore, accurate pathological assignment to either stage T1a or T1b is crucial for selection of appropriate management options. A variety of methods for staging patients with incidentally detected prostate cancer have been proposed, including detailed histological analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic resonance (MRI) techniques. This article critically examines the clinical utility of these staging modalities for patients with incidentally detected prostate cancer.     

Target differentiation with simple infrared sensors using statistical pattern recognition techniques

This study compares the performances of various statistical pattern recognition techniques for the differentiation of commonly encountered features in indoor environments, possibly with different surface properties, using simple infrared (IR) sensors. The intensity measurements obtained from such sensors are highly dependent on the location, geometry, and surface properties of the reflecting feature in a way that cannot be represented by a simple analytical relationship, therefore complicating the differentiation process. We construct feature vectors based on the parameters of angular IR intensity scans from different targets to determine their geometry and/or surface type. Mixture of normals classifier with three components correctly differentiates three types of geometries with different surface properties, resulting in the best performance (100%) in geometry differentiation. Parametric differentiation correctly identifies six different surface types of the same planar geometry, resulting in the best surface differentiation rate (100%). However, this rate is not maintained with the inclusion of more surfaces. The results indicate that the geometrical properties of the targets are more distinctive than their surface properties, and surface recognition is the limiting factor in differentiation. The results demonstrate that simple IR sensors, when coupled with appropriate processing and recognition techniques, can be used to extract substantially more information than such devices are commonly employed for.     

Synthesis and comparative molecular field analysis (CoMFA) of antitumor 3-arylisoquinoline derivatives

In this study a series of 3-arylisoquinoline derivatives were synthesized and cytotoxicity against human melanoma tumor cell evaluated, and a three dimensional quantitative structure-activity relationship was investigated using the comparative molecular field analysis (CoMFA). The results suggested that the electrostatic, steric and hydrophobic factors of 3-arylisoquinolines were strongly correlated with the antitumor activity. Considerable predictive ability (cross-validated r2 as high as 0.721) was obtained through CoMFA.     

Lithium-induced follicular hyperkeratosis

Scanning with Tc-99m labeled RBC was performed in two patients with recurrent postoperative gastrointestinal bleeding after partial colonic resection. Imaging correctly identified the source of bleeding at the anastomotic site in the large bowel, effectively contributing in the patient's treatment planning. Radionuclide scintigraphy provides a simple, noninvasive modality to diagnose and manage difficult clinical situations such as postoperative bleeding.