Increased glucocorticoid activity in men with cardiovascular risk factors

The association between hypertension and insulin resistance might be explained by increased activity of the principal glucocorticoid, cortisol. Recent data show that the intensity of dermal vasoconstriction after topical application of glucocorticoids is increased in patients with essential hypertension. In this report, we examine whether increased glucocorticoid sensitivity or secretion is associated with insulin resistance and is a cause or consequence of hypertension. We studied 32 men (aged 47 to 56 years) from a cross-sectional study and 105 men (aged 23 to 33 years) in whom predisposition to high blood pressure has been defined by their own blood pressure and the blood pressures of their parents. In both populations, increased dermal glucocorticoid sensitivity was associated with relative hypertension, insulin resistance, and hyperglycemia. In young men with higher blood pressure whose parents also had high blood pressure, enhanced glucocorticoid sensitivity was accompanied by enhanced secretion of cortisol, enhanced ligand-binding affinities for dexamethasone in leukocytes, and impaired conversion of cortisol to inactive metabolites (cortisone and 5beta-dihydrocortisol). Increased tissue sensitivity to cortisol, amplified by enhanced secretion of cortisol, is a feature of the familial predisposition to high blood pressure rather than a secondary effect of high blood pressure. It may be mediated by an abnormal glucocorticoid receptor, and it may contribute to the association between hypertension and insulin resistance.     

Reliability and validity of the interview and self-report versions of the BASIS-32

The psychometric properties of the interview and self-report versions of the BASIS-32 were compared. A total of 120 severely mentally ill adults enrolled in psychosocial rehabilitation were randomly assigned to either a self-report or an interview condition. The BASIS-32 had good internal consistency and test-retest reliability on most subscales; coefficients were higher in the self-report condition. Only the interview version of the psychosis subscale had unacceptable internal consistency. Validity correlations were generally good for the symptom subscales but disappointing for the functional domains. The subscale scores did not discriminate between diagnostic subgroups.     

Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of viral replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.     

氯酸和碱金属氯酸盐混合物及二氧化氯的制备

在电解槽里生产了氯酸和碱金属氯酸盐的水溶液,电解槽中有一个阳极室、一个阴极室及在阳极室与阴极室之间的至少一个离子交换室。该过程如下：送碱金属氯酸盐的水溶液到离子交换室,在阳极室里电解阳极液产生氢离子,从阳极室传递氢离子通过阳离子交换膜进入离子交换室置换碱金属离子,并产生氯酸和碱金属氯酸盐的水溶液,从离子交换室传递碱金属离子进入阴极室,从离子交换室排出氯酸和碱金属氯酸盐的水溶液,而且,增加氯酸盐离子     

Geometric characterization of stenosed human carotid arteries

RATIONALE AND OBJECTIVES: The geometry of stenosed carotid bifurcations was analyzed to determine average representations for several stenosis grades. METHODS: Film angiograms of 62 patients with internal carotid artery stenoses were digitized. Residual lumen boundaries were manually outlined. The outlines were processed with a computer to extract geometric measurements. The measurements were grouped according to stenosis grade and used to create average representations. RESULTS: Accuracy and precision of the outlining technique were +/- 0.020 common carotid diameters (CCD) and +/- 0.025 CCD, respectively. Maximum narrowing of the internal carotid artery occurred at 0.3 CCD +/- 1.5 (mean +/- standard deviation) distal to the flow divider. The region of significant narrowing extended axially 1.2 CCD +/- 1.0. Poststenotic dilatations were observed, with enlargement of 1.3 +/- 0.7 times the normal diameter of the distal internal carotid artery. A tendency toward smaller bifurcation angles with increasing stenosis severity was observed. CONCLUSION: Three-dimensional geometric models could be created for carotid bifurcations that were disease free (normal) and of arbitrary stenosis grade.     

A carcinogenesis model describing mutational events at the DNA adduct level

A stochastic carcinogenesis model is proposed to describe a sequence of component mutational changes that constitute the G:C-->A:T base substitution. This paper provides the biological basis and mathematical formulation underlying the proposed model. In addition, the paper elaborates on a numerical approach for studying the cumulant functions, survival functions, and hazard functions of the model. Several numerical examples are given of potential applications of the model.     

Pharmacologic actions of the second-generation leukotriene B4 receptor antagonist LY293111: in vitro studies

The in vitro actions were investigated of LY293111, a potent and selective leukotriene B4 (LTB4) receptor antagonist, on human neutrophils, human blood fractions, guinea pig lung membranes, and guinea pig parenchymal and tracheal strips. The IC50 for inhibiting [3H]LTB4 binding to human neutrophils was 17.6 +/- 4.8 nM. LY293111 inhibited LTB4-induced human neutrophil aggregation (IC50 = 32 +/- 5 nM), luminol-dependent chemiluminescence (IC50 = 20 +/- 2 nM), chemotaxis (IC50 = 6.3 +/- 1.7 nM), and superoxide production by adherent cells (IC50 = 0.5 nM). Corresponding responses induced by N-formyl-L-methionyl-L-leucyl-L-phenylalanine were inhibited by 100-fold higher concentrations of LY293111. LTB4 binding to guinea pig tissues and subsequent activation were also inhibited. The Ki for inhibition of [3H]LTB4 binding to lung membranes was 7.1 +/- 0.8 nM; IC50 for preventing binding of [3H]LTB4 to spleen membranes was 65 nM. The compound inhibited LTB4-induced contraction of guinea pig lung parenchyma. At 10 nM, LY293111 caused a parallel rightward shift of the LTB4 concentration-response curve. At higher concentrations, plots were shifted in a nonparallel manner, and maximum responses were depressed. LY293111 did not prevent antigen-stimulated contraction of sensitized trachea strips. At micromolar concentrations, LY293111 inhibited production of LTB4 and thromboxane B2 by plasma-depleted human blood stimulated with N-formyl-L-methionyl-L-leucyl-L-phenylalanine and thrombin. In addition, at these higher concentrations, formation of LTB4 by A23187-activated whole blood and conversion of arachidonic acid to LTB4 by a human neutrophil cytosolic fraction were inhibited. In summary, LY293111 is a second-generation LTB4 receptor antagonist with much improved potency in a variety of functional assay systems.     

Neural networks for the analysis of small pulmonary nodules

PURPOSE: Small pulmonary nodules can be readily detected by computed tomography (CT). The goal of this detection is to diagnose early lung cancer as the five year survival at this early stage is over 70% in contradistinction to the overall 5-year survival of around 10%. Critical to the efficacy of CT for early lung cancer detection is the ability to distinguish between benign and malignant nodules. We explored the usefulness of neural networks (NNs) to help in this differentiation. METHODS: CT images of 28 pulmonary nodules, 14 benign and 14 malignant, each having a diameter less than 3 cm were selected. All were sufficiently malignant in appearance to require needle biopsy and surgery. The statistical-multiple object detection and location system (S-MODALS) NN technique developed for automatic target recognition (ATR) was used to differentiate between these benign and malignant nodules. RESULTS: S-MODALS was able to correctly identify all but three benign nodules. S-MODALS classified a nodule as malignant because it looked similar to other malignant nodules. It identified the most similar nodules to display them to the radiologist. The specific features of the nodule that determined its classification were also shown, so that S-MODALS is not simply a "black box" technique but gives insight into the NN diagnostics. CONCLUSION: This initial evaluation of S-MODALS NNs using pulmonary nodules whose CT features were very suspicious for lung cancer demonstrated the potential to reduce the number of biopsies without missing malignant nodules. S-MODALS performed well, but additional optimization of the techniques specifically for CT images would further enhance its performance.