The patient with CHD: how should we translate international guidelines into clinical practice?
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Biomedical subjects
Publications and source records attributed to M Mancini.
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BACKGROUND: The Gubbio study is an Italian population study which measures the risk factors and incidence of major cardiovascular diseases. This analysis produces multivariate models for the prediction of cardiovascular end-points. METHODS: A population sample of 2,963 men and women aged 35-74, free from major cardiovascular diseases, was examined in 1983 with risk factor measurement, and a 6-year incidence was computed for coronary heart disease and all cardiovascular (atherosclerotic) events. Proportional hazards models were solved for the prediction of these events. RESULTS: Over a 6-year period, 74 hard criteria, and 126 any criterion coronary heart disease and 174 cardiovascular events were recorded. Multivariate models showed the predictive power of sex (relative risk ranging 1.63 to 2.60), age (relative risk for 5-year difference ranging 1.38 to 1.48), systolic blood pressure (relative risk for 20 mmHg difference ranging 1.17 to 1.27), HDL cholesterol (relative risk for a difference of 10 mg/dl ranging 0.73 to 0.81), non-HDL cholesterol (relative risk for 40 mg/dl difference ranging 1.15 to 1.27), cigarette smoking (relative risk for 10 cigarette difference ranging 1.21 to 1.28), and body mass index (relative risk for 3 units ranging 0.99 to 1.02). All coefficients were statistically significant except that for body mass index, they were larger for hard criteria coronary heart disease, and their magnitude was similar to that found in previous Italian population studies. CONCLUSIONS: Traditional cardiovascular risk factors predict coronary and cardiovascular events in another Italian population study confirming previous findings and similar predictive models.
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Hibernomas are rare soft tissue tumors of brown fat differentiation. A case of a large axillary hibernoma, along with a review of its pathology, is presented. This tumor matches the largest hibernoma in the literature and is the largest in an axillary site.
Human neutrophils incubated with the anti-HLA-DR mAb Lym-1, plus PMA, induced significant cytolysis of B lymphoma cells compared with Lym-1 and PMA alone. The effect of PMA was independent of the ability of the compound to stimulate neutrophil-respiratory burst. In fact, first, neutrophils from a patient with chronic granulomatous disease were cytolytically effective in spite of their inability to produce oxidants. Second, various kinase inhibitors exerted different effects on the PMA-stimulated cytolytic system and neutrophil-oxidative burst. Previous studies have shown the involvement of the FcgammaRII, CD11b-CD18 integrins, and CD66b glycoproteins in the Lym-1 mAb-dependent cytolysis by GM-CSF-stimulated neutrophils. The present PMA-stimulated system was inhibited by the anti-FcgammaRII mAb IV.3, the anti-CD18 mAb MEM 48, and the anti-CD11b mAb 2LPM19c but not by the anti-CD66b mAb 80H3 and N-acetyl-D-glucosamine. Furthermore, the PMA- and GM-CSF-stimulated cytolysis was insensitive and sensitive to inhibition by pertussis toxin, respectively. Thus, the use of PMA and GMCSF as neutrophil stimulants uncovers the existence of distinct mechanisms of Lym-1 mAb-mediated cytolysis.
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The aim of this paper is to evaluate whether echo-color Doppler diagnostics allows to detect the different evolutionary stages of arteriopathy affecting the cavernous arteries of the penis. 124 patients with erectile deficiency were examined. All of them were evaluated by andrologic and psychologic anamnesis. An echo-color Doppler examination was performed on cavernous arteries before (basal) and after (dynamic) an injection of Prostaglandin E1 (10 micrograms). The penile circulation has been observed for twenty minutes after the injection to detect anomalous collateral vessels of the cavernous arteries. The population was divided into 4 groups according to the basal and dynamic peak systolic velocity (PSV). Cardiovascular risk factor incidence in patients with normal basal and dynamic PSV values (group A) and in patients with pathologic basal and dynamic PSV values (group C) is 10% and 44% respectively (p < 0.002). Psychologic disorder in group A and C is 41% and 26% respectively (p < 0.05). Patients with pathologic basal PSV and normal dynamic PSV (group B) show an intermediate (26%) incidence of cardiovascular disorders as compared to A and C. Anomalous side branches are equally represented in A and B (41% and 38%) and to a lesser extent in C (26%). Based on anamnestic and instrumental data, Group B ranges at an intermediate position between A and C. In this group, the presence of incipient arteriopathy affecting the penile circulation may be suspected. The ability to detect patients with vascular diseases still at a subclinical stage, as it already happens for other organs, would allow a prompt therapeutic action.
We have generated a panel of 20 somatic cell hybrids retaining fragments of human chromosome 12. Each hybrid was characterized cytogenetically by reverse fluorescence in situ hybridization (FISH) and molecularly by 24 sequence tagged sites (STSs) spaced evenly along the chromosome. The panel can be exploited to map subregionally DNA sequences on chromosome 12 and to generate partial chromosome paints useful in the characterization of chromosomal rearrangements involving this chromosome. Furthermore, a panel of 58 yeast artificial chromosomes (YACs) mapping to chromosome 12 was characterized by FISH experiments on normal human metaphases. A subset of this panel is recognized by the STSs used in the somatic cell hybrid characterization. In this way a correlation between the genetic and the physical maps of this chromosome can be established.
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The injection of plasmid DNA encoding hepatitis B virus (HBV) envelope proteins in mouse muscle leads to the induction of specific humoral and cellular immune responses. Most studies on DNA-based immunization have used viral promoters to drive antigen expression. In this study, we compared the efficiency of a muscle-specific promoter, the human desmin gene promoter, with the commonly used cytomegalovirus (CMV) early gene promoter. We showed that increased in vitro expression of HBV envelope proteins from the human desmin gene promoter has no effect on the in vivo immune response even after the injection of as little as 10 micrograms of DNA. The injection of vectors encoding HBV envelope proteins under the control of either the human desmin gene promoter or the CMV promoter induced humoral and cytotoxic immune responses at comparable levels and of the same duration. The recruitment of antigen-presenting cells to the DNA injection site by pretreatment of muscle with a necrotizing agent increases the precocity and the intensity of the responses, particularly when the nonspecific CMV vector was used.
Intramuscular injection of a plasmid encoding a modified hepatitis B surface antigen (HBsAg) induced humoral and cytotoxic responses in C57BL/6 mice. This modified HBsAg contains a preS1-derived peptide (amino acids 21 to 47), that carries the HBV receptor binding site for hepatocytes fused to the C-terminus of the small protein (at the position of amino acid 223). After a single DNA injection, the immunized mice elicited high titers of anti-HBs and anti-preS1 antibodies, and produced strong HBV specific cytotoxic T-lymphocyte (CTL) responses. The immune response induced after a single injection of this modified HBsAg gene in HBsAg-transgenic mice resulted in the clearance of circulating HBsAg and the appearance of anti-HBs and anti-preS1 antibodies. The high titers of preS1 antibody in transgenic mice were comparable to those found in non-transgenic controls and may be efficient to clear Dane particles existing in sera from chronic carriers. These data indicated that a genetic vaccine consisting of this modified HBsAg gene may have a potential use for both prophylactic and therapeutic purposes.
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OBJECTIVE AND DESIGN: In the present work, we studied the role of cell-derived adenosine in both the physiologic regulation and pharmacologic control of the exocytosis of azurophilic granules of neutrophils exposed to tumor necrosis factor alpha (TNF) and stimulated with some chemoattractants. MATERIAL AND METHODS: Human neutrophils were pre-incubated in the absence or presence of TNF. Thereafter, the appropriate chemoattractant was added to the cells. After incubation, the cell-free supernatant was collected for testing elastase activity and intracellular cAMP levels. Results, expressed as mean +/- 1 SD, were evaluated by unpaired, two-tailed Student's t-test and by analysis of variance followed by Student-Newman-Keuls multiple comparisons test. RESULTS: Neutrophil incubation with 10 ng/ml TNF or 0.1 micromol/l N-formyl-met-leu-phe (fMLP) failed to release elastase activity (NE) (NE in absence of stimulus: 23.1 +/- 5.7 nmol/h; TNF-induced NE: 26.4 +/- 14.4 nmol/h; fMLP-induced NE: 27.0 +/- 9.9 nmol/h). Neutrophils, pre-exposed to various amounts of TNF, released elastase in response to 0.1 micromol/l fMLP in a dose-dependent manner (NE in presence of 10 ng/ml TNF and 0.1 micromol/l fMLP: 133.7 +/- 24.0 nmoles/h). As compared with fMLP, C5a had lower activity (NE in presence of 10 ng/ml TNF and 0.1 micromol/l C5a: 66.4 +/- 25.1 nmoles/h), whereas interleukin-8, platelet activating factor and leukotriene B4 were ineffective. The secretory response of TNF-primed neutrophils to fMLP was inhibited by adenosine in a dose-dependent manner (IC50 = 5.18 +/- 7.1 micromol/l). The addition of adenosine deaminase (ADA) to TNF-primed neutrophils resulted in increased secretory response to fMLP (NE in absence and presence of 0.25 U/ml ADA: 71.5 +/- 11.0 and 107.3 +/- 18.6 respectively, P = 0.060). Moreover, two inhibitors of phosphodiesterase type IV (RO 20-1724 and nimesulide) reduced the elastase release only in the absence of ADA (RO 20-1724: percent inhibition in absence or presence of ADA = 20.2 +/- 15.0 and 4.4 +/- 5.1 respectively; nimesulide: percent inhibition in absence or presence of ADA = 22.2 +/- 19.6 and 0.8 +/- 3.0 respectively). Similarly, RO 20-1724 and nimesulide increased intracellular cAMP levels only in absence of ADA (RO 20-1724: percent cAMP increment in absence or presence of ADA = 215.4 +/- 97.5 and 47.3 +/- 53.3 respectively; nimesulide: percent cAMP increment in absence or presence of ADA = 177.7 +/- 19.0 and 19.5 +/- 29.3 respectively). CONCLUSIONS: Endogenous adenosine down-regulates the cell secretory response and is instrumental in uncovering the susceptibility of azurophilic granule exocytosis to control by inhibitors of phosphodiesterase type IV.
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The annual meeting of the American Society for Cell Biology (ASCB) is a large and diverse gathering. At last year's meeting**The American Society for Cell Biology 38th Annual Meeting, San Francisco, USA; 12-16 December, 1998. Program chair: Jennifer Lippincott-Schwartz., there were over 8000 attendees, and the topics discussed covered many areas of cell biology. It would be impossible to cover the entire meeting within a trends in CELL BIOLOGY report, so instead we are focusing on an aspect of it that provided some of the most interesting and fruitful discussions. On Saturday afternoon, before the main symposia began, there were 11 special-interest subgroup meetings. The atmosphere at these meetings was informal, and they encouraged open and frank discussion of data and issues. This report provides a brief summary of the discussions at seven of the special-interest subgroup meetings.
Human neutrophils, incubated with Cr51-labelled B lymphoblastoid Raji cells in the presence of the anti-target monoclonal antibody (mAb) Lym-1 plus formyl-methionyl-leucyl-phenylalanine (FMLP) or tumour necrosis factor alpha (TNF-alpha), were found to induce significant C51 release, i.e. significant cytolysis. The lytic process was inhibited by mAb IV.3, specific for the Fcgamma receptor (FcgammaR) type II. The mAb 3G8, which reacts with FcgammaR type III, was ineffective. Moreover, the lysis was inhibited by the anti-CD18 mAb MEM-48. These data suggest that FMLP/Lym-1 as well as TNF-alpha/Lym-1 cytolytic systems strictly require FcgammaRII and CD18 integrins. As the lysis induced by TNF-alpha/Lym-1 was prevented by pertussis toxin (PT), PT-sensitive G-proteins are likely to intervene in post-FcgammaRII signal transduction. Both the FMLP- and the TNF-alpha-dependent systems were also found to be equally susceptible to inhibition by various inhibitors of kinases (genistein, staurosporin, 1-(5-isoquinolinnylsulphonyl)-2-methylpiperazine and wortmannin). On the contrary, an inhibitor of protein kinase C (bis-indolyl-maleimide, BIM) was effective only in the FMLP/Lym-1 cytolytic system. Therefore, it appears that signals delivered by FMLP or TNF-alpha, BIM-sensitive and insensitive respectively, converge and synergize with those from G-protein-coupled FcgammaRII and, probably, CD18-integrins to promote the expression of the neutrophil cytolytic potential.
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