Optimization of parameters for the detection of cerebral aneurysms: CT angiography of a model

PURPOSE: To optimize parameters with computed tomographic angiography for the detection of cerebral aneurysms. MATERIALS AND METHODS: Model aneurysms were placed randomly at various branch points and scanned multiple times with spiral technique. The final analysis included 63 branch points and 22 aneurysms. Each spiral scan used a different parameter combination. Collimation ranged from 1.5 to 4.0 mm and pitch ranged from 1:1 to 1.5:1. Images were constructed with shaded surface display (SSD) and maximum intensity projection (MIP) algorithms and were interpreted by three readers for the presence or absence of aneurysm. RESULTS: The receiver operating characteristic (ROC) curve area for 1.5-mm collimation was greater than those of 3- or 4-mm collimation (P < .01 and P < .001, respectively). There was no statistically significant difference in the ROC curve areas between 3- and 4-mm collimation (P = .37). There was no statistically significant decrease in ROC curve area when increasing pitch from 1:1 to 1.5:1 for any value of collimation (P = .96). For all parameter combinations the ROC curve areas for SSD images was greater than that of MIP images (P < .0001). CONCLUSION: For cerebral aneurysm detection, narrow collimation is superior to wider collimation. Mild increases in pitch do not substantially degrade diagnostic accuracy. SSD offers improved diagnostic accuracy over MIP display in this model.     

17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1B1

The 4-hydroxy metabolite of 17 beta-estradiol (E2) has been implicated in the carcinogenicity of this hormone. Previous studies showed that aryl hydrocarbon-receptor agonists induced a cytochrome P450 that catalyzed the 4-hydroxylation of E2. This activity was associated with human P450 1B1. To determine the relationship of the human P450 1B1 gene product and E2 4-hydroxylation, the protein was expressed in Saccharomyces cerevisiae. Microsomes from the transformed yeast catalyzed the 4- and 2-hydroxylation of E2 with Km values of 0.71 and 0.78 microM and turnover numbers of 1.39 and 0.27 nmol product min-1.nmol P450-1, respectively. Treatment of MCF-7 human breast cancer cells with the aryl hydrocarbon-receptor ligand indolo[3,2-b]carbazole resulted in a concentration-dependent increase in P450 1B1 and P450 1A1 mRNA levels, and caused increased rates of 2-, 4-, 6 alpha-, and 15 alpha-hydroxylation of E2. At an E2 concentration of 10 nM, the increased rates of 2- and 4-hydroxylation were approximately equal, emphasizing the significance of the low Km P450 1B1-component of E2 metabolism. These studies demonstrate that human P450 1B1 is a catalytically efficient E2 4-hydroxylase that is likely to participate in endocrine regulation and the toxicity of estrogens.     

Combined cis-platinum and alpha interferon therapy of advanced hepatocellular carcinoma

To evaluate the clinical efficacy of alpha-interferon(IFN-alpha) plus cis-platinum in hepatocellular carcinoma(HCC). 56 inoperable patients with HCC were divided into IFN-alpha plus cis-platinum treated group (n = 30) and no antitumor therapy group (n = 26). The survival of IFN-alpha plus cis-platinum treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.001). Median survival time was 33 weeks and 14.0 weeks, respectively. The cumulative estimated survival rates of our IFN-alpha plus cis-platinum treated group (93.5% at 3mo, 75.0% at 6mo) were for longer than that of the no antitumor therapy group (84.6% at 3mo, 57.7% at 6mo). Objective tumor regression, greater than 50% was observed in 13.3% (4 of 30) of patients receiving IFN-alpha plus cis-platinum. By the univariate analysis, the absence of portal vein thrombus (p < 0.05), alkaline phosphatase lesser than 280 U/L (p = 0.001), total bilirubin less than 2.0 mg% (p < 0.05), serum triglyceride less than 155 mg/dl (p < 0.05) were shown to be the factors most significantly favoring a better survival. By the multivariate analysis, using Cox proportional hazards model, IFN-alpha plus cis-platinum treated group (p = 0.0001), alkaline phosphatase less than 280 mg/dl (p = 0.005), the absence of portal vein thrombus (p = 0.020) were independent favorable prognostic factors. We conclude that IFN-alpha plus cis-platinum is useful in patients with inoperable HCC and the above favorable prognostic factors may also be useful in the design and analysis of future clinical trials of systemic chemotherapy for HCC.     

The impact of breast cancer on sexuality

An eleven year old boy presented with sudden onset right-sided hemiplegia and ipsilateral lower facial weakness. Two-dimensional echo revealed the diagnosis of idiopathic dilated cardiomyopathy with multiple intracardiac clots. MRI scan of head showed infarctions in the area of caudate nuclei, putamen, brain stem and cerebellum. On anticoagulation therapy, all thrombi, except one, disappeared. The child died 2.5 months later due to resistant cardiac failure.     

Opposite effects of bezafibrate and gemfibrozil in both normal and hypertriglyceridemic rats

The diagnostic value of zinc protoporphyrin (ZPP) as an indicator of iron-deficient anemia (IDA) in hospitalized patients is assessed in this study. ZPP was measured using an AVIV hematofluorometer with a coefficient of variation (CV) less than 5% and a recovery of greater than 97%. A reference range of 53-70 mu mol/mol heme was determined for ZPP in non-anemic patients in a hospital population. Hospitalized patients (221) with low hemoglobin (< 120 g/l) were evaluated for their iron status. ZPP and other anemia tests were performed. Macrocytic patients with mean corpuscular volume (MCV) greater than 98 fl) were excluded from the study. Seventy-four microcytic patients (MCV < 80 fl) were determined as having IDA according to a diagnostic algorithm. A distribution study of these microcytic patients showed that there was a significant overlap of values between the IDA and non-IDA patients for all serum anemia tests. A receiver-operator curve analysis revealed that ZPP has a relatively high degree of diagnostic efficiency better than iron and ferritin for this patient population. At a cutoff value > 170 mu mol/mol heme, ZPP has a sensitivity of 93% and a specificity of 90%. In addition, ZPP is also elevated in normocytic patients (MCV = 80-98 fl) with low ferritin values, who may have iron depletion. From these data, it is proposed that ZPP may be used as a screening tool for IDA in hospitalized patients.     

Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells

Sulfur dioxide (SO2) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials after a 4-hr incubation period. The net nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)     

Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2

Low pH enhances tumor necrosis factor alpha (TNF)-induced cytolysis of cancer cells and TNF-membrane interactions that include binding, insertion, and ion-channel formation. We have also found that TNF increases Na+ influx in cells. Here, we examined the structural features of the TNF-membrane interaction pathway that lead to channel formation. Fluorometric studies link TNF's acid-enhanced membrane interactions to rapid but reversible acquisition of hydrophobic surface properties. Intramembranous photolabeling shows that (i) protonation of TNF promotes membrane insertion, (ii) the physical state of the target bilayer affects the kinetics and efficiency of TNF insertion, and (iii) binding and insertion of TNF are two distinct events. Acidification relaxes the trimeric structure of soluble TNF so that the cryptic carboxyl termini, centrally located at the base of the trimer cone, become susceptible to carboxypeptidase Y. After membrane insertion, TNF exhibits a trimeric configuration in which the carboxyl termini are no longer exposed; however, the proximal salt-bridged Lys-11 residues as well as regional surface amino acids (Glu-23, Arg-32, and Arg-44) are notably more accessible to proteases. The sequenced cleavage products bear the membrane-restricted photoreactive probe, proof that surface-cleaved TNF has an intramembranous disposition. In summary, the trimer's structural plasticity is a major determinant of its channel-forming ability. Channel formation occurs when cracked or partially splayed trimers bind and penetrate the bilayer. Reannealing leads to a slightly relaxed trimeric structure. The directionality of bilayer penetration conforms with x-ray data showing that receptor binding to the monomer interfaces of TNF poises the tip of the trimeric cone directly above the target cell membrane.