[Prevention of venous thromboembolism: controversies on the table].
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Fibrinolytic Agents↗
Biomedical subjects
S Fontana
Publications and source records attributed to S Fontana.
Linear transgene constructs lacking vector backbone sequences generate low-copy-number transgenic plants with simple integration patterns.
Whole plasmids are used in both Agrobacterium-mediated transformation and direct DNA transfer, generally leading to the integration of vector backbone sequences into the host genome along with the transgene(s). This is undesirable, as vector backbone sequences often have negative effects on transgene or endogenous gene expression, and can promote transgene rearrangements. We, therefore, bombarded rice tissue with two constructs: a plasmid containing the bar gene, and a linear DNA fragment isolated from the same plasmid, corresponding to the minimal bar gene expression cassette (promoter, open reading frame and terminator). We recovered phosphinothricin-resistant plants from both experiments, showing that the selectable marker was efficiently expressed. Transformation with such constructs resulted in predominantly 'simple' integration events (one or two bands on Southern blots), producing low-copy-number transgenic plants with a low frequency of transgene rearrangements. Conversely, transformation with supercoiled or linearized whole plasmids generated plants with 'complex' integration patterns, that is, higher copy numbers and frequent transgene rearrangements. We monitored transgenic lines through to the R4 generation and observed no silencing in plants carrying minimal constructs. We also carried out experiments in which rice tissue was simultaneously bombarded with minimal linear hpt and gusA cassettes. We observed robust GUS activity in hygromycin-resistant plants, confirming co-expression of the selectable and nonselectable markers. Furthermore, the efficiency of cotransformation using minimal constructs was the same as that using supercoiled plasmid cointegrate vectors.
Acetyltransferases↗
HLA class I antigen downregulation by interleukin (IL)-10 is predominantly governed by NK-kappaB in the short term and by TAP1+2 in the long term.
The present study was designed to determine the molecular mechanisms by which interleukin (IL)-10 prevents the HLA class I antigen expression at the cell surface. In this context, the potential role of transporter associated with antigen presentation 1+2 (TAP1+2) molecules and NF-kappaB transcription factors was addressed. The IL-10 effect was investigated in a human lymphoblastoid cell system defective for TAP1+2 genes (T2 cell line) and in the related TAP1+2 transfectants (T3 cell line). In this experimental system, after 48 h of incubation in the presence of IL-10, the HLA class I antigen downmodulation was observed in the T3 but not in the T2 cell line, suggesting a potential role of TAP1+2 molecules. In the same experimental conditions, the NF-kappaB activity was unaffected. Instead, after 3 h of exposure to IL-10, the HLA downmodulation was observed in both cell lines, the NF-kappaB factors activity being strongly reduced. In addition, the transfection of the inhibitor of NF-kappaB, IkappaBalpha, prevented the IL-10 effect on HLA class I antigen expression in the T3 cell line. This phenomenon was observed after 3 h but not 48 h of IL-10 incubation. These evidences indicate a time dependent involvement of TAP1+2 antigens and of NF-kappabeta activity in the IL-10-induced major histocompatibility complex (MHC) class I downmodulation.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis.
Pelvic endometriosis is an immune-related chronic inflammatory disease, characterized by ectopic implants of endometrium in the peritoneal cavity and associated with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin itself can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. We investigated whether leptin concentrations in serum and peritoneal fluid (PF) differed between 13 patients with different stages of endometriosis and 15 age- and body mass index-matched controls. We found a statistically significant (P < 0.05) increase in leptin levels in serum (30.3 +/- 14.8 ng/mL) and PF (35.9 +/- 17.4 ng/mL) of patients with endometriosis, compared with our control population (serum, 15.6 +/- 8.4; PF, 17.5 +/- 7.2 ng/mL). Regression equations, relating leptin to body mass index, were also significantly different in endometriosis patients, compared with controls. Higher levels of leptin were observed in the earlier stages of endometriosis than advanced-stage disease. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis.
Adult↗
Role of iron in asbestos-body-induced oxidant radical generation.
Asbestos bodies (AB) were harvested from human lung tissue digests and isolated from uncoated asbestos fibers. Samples containing 1000 AB were added to a reactive solution to investigate the ability of AB to oxidize deoxy-D-ribose and generate reactive oxygen species (ROS) in the presence of ascorbate and hydrogen peroxide as determined by formation of thiobarbituric acid (TBA)-reactive products. Three types of asbestos fibers were tested for comparison, since they are known to be able to produce ROS. The absorbance values measured with 1000 AB were significantly higher than those observed with 1000 fibers of the three types of asbestos. Since in our reaction system the only source of transition metals was the iron-rich AB, data suggest iron derived from the ferritin coating of AB was involved in oxidant generation. Addition of iron to AB enhanced TBA-reactive product formation, while chelation of Fe with deferoxamine reduced this reaction. Hydroxyl radical scavengers 1,3-dimethyl-2-thiourea (DMTU) and mannitol (MN) also effectively blocked TBA-reactive product generation. Data indicate the importance of Fe in AB-induced oxidant damage. With the addition of polymorphonuclear leukocytes (PMN) to AB, incubation in the reactive solution gave very high amounts of TBA-reactive products, but using a reactive solution devoid of ascorbate, very low amounts of TBA-reactive products were generated. In the latter condition, the superoxide of cell membranes probably reduced and removed iron from AB-coating ferritin, but less effectively than ascorbate. Further after the possible reoxidation of Fe2+, Fe3+ could be coordinated by lactoferrin. Since such availability of reductant is never approached in living systems, the iron in the AB coating is unlikely to function as a catalyst of Fenton-type reactions in vivo.
Asbestos↗
Daily hunger sensation and body compartments: II. Their relationships in obese patients.
Hunger sensation (HS) is a signal whose levels change during the 24-h day. The daily mean level of HS was correlated with the human body compartments, as investigated by bioelectrical impedance analysis, to detect the relationship between the orectic perception and both the free fat mass (FFM) and the fat body mass (FBM) in 22 clinically healthy subjects (CHS) (2 M, 20 W, BMI: 18.5-24.0 kg/m2) and 48 obese patients (OP) (4 M, 44 W, BMI: 25.2-54.7 kg/m2). In CHS, the daily mean level of HS correlated positively with the FFM and negatively with the FBM. These correlations were not present in OP. This lack of relationships between HS and the body compartments where energy is maximally consumed (i.e., the FFM) and maximally stored (i.e., the FBM) indicates that the orectic response to energy expenditure and the orectic inhibition to fat accumulation are feedback mechanisms which are impaired in obesity.
Adipose Tissue↗
Anxiety, depression, hunger and body composition: III. Their relationships in obese patients.
The present paper explores the relationships between anxiety, depression, hunger sensation and body composition in obese patients (OP). The aim is to detect whether or not there are abnormalities in these relationships in OP as compared to clinically healthy subjects (CHS). The study was performed on 22 CHS (2 M, 20 W; mean age = 24 +/- 2 years; mean body mass index = 21 +/- 2 kg/m2) and 48 OP (4 M, 44 W; mean age = 40 +/- 17 years; mean body mass index = 32 +/- 7 kg/m2). Anxiety and depression were found to be correlated, negatively, with the relative lean body mass, and, positively, with the fat body mass in OP but not in CHS. These findings corroborate the idea that anxiety and depression can reach an abnormal expression when obesity shows its worst loss in lean body mass and its highest expansion in adipocyte mass. As hunger sensation was found not to correlate with either anxiety or depression in OP, the opinion is expressed that the impairment of anxio-depressive integrity is a corollary of obesity rather than a primary affective disorder leading to obesity via an enhanced food intake.
Adult↗
[Derailed oral anticoagulation with very high INR values and poor response to oral vitamin K--cholestasis as a possible cause].
A 76-year-old man under long term oral anticoagulant treatment showed unclottable prothrombin time (PT) without overt bleeding. After oral administration of vitamin K1, PT remained severely prolonged and the patient was hospitalized. INR was 8.0 and responded to parenteral vitamin K. Cholestasis resulting in poor intestinal vitamin K resorption was assumed to have caused "overanticoagulation". Quick test is a global clotting test for the extrinsic and common pathways of the coagulation system. Increased PT, i.e. decreased Quick percentage, may be due to different conditions and should--if unexplained--be further analyzed by assaying factors II, V, VII, X and fibrinogen. Preanalytical problems, plasma dilution with clotting factor-free volume replacement, decreased vitamin K-dependent clotting factors (oral anticoagulation, intoxication with certain rodenticides, vitamin K deficiency), impaired liver synthetic capacity, disseminated intravascular coagulation, or massive heparin contamination may cause prolonged PT. Newborns physiologically have longer PT and should receive vitamin K prophylaxis.
Administration, Oral↗
[Chronic, hemorrhage-induced iron deficiency anemia in Osler disease].
We report the history of a 77-year-old man with Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia) who suffered from recurrent epistaxis and chronic bleeding anemia for many years. Hereditary hemorrhagic telangiectasia is a rare congenital disease, that is characterized by telangiectases of the nasal and oral mucosa, the gastrointestinal tract and the skin. Arteriovenous malformations of the lung and the brain may be present. The genetic and pathologic features, the clinical manifestations and the differential diagnosis are shortly presented. The management is not validated by controlled studies and is mainly based on clinical experience. It involves supportive therapy with iron supplementation and erythrocyte transfusions, if needed, for chronic bleeding anemia, aminocaproic acid, tranexamic acid or oestrogen-progesterone therapy to prevent mucosal bleeding, cauterisation, photocoagulation, transcatheter embolotherapy or surgery to treat the vascular abnormalities.
Aged↗
Hunger sensation: a chronobiometric approach to its within-day and intra-day recursivity in anorexia nervosa restricting type.
Hunger sensation (HS) is a perception with a daily (circadian) and within-day (ultradian) recursive pattern. In human beings, circadian repeatability was investigated by means of the Single Cosinor method, while the ultradian recursivity was investigated by means of the spectral analysis, both applied to the 24-h HS profile (orexigram). Orexigrams were provided by each subject investigated, who self-rated her subjective orectic stimulus (OS) (from 1 to 10 hunger units) every half hour. The study was performed in 19 female patients aged 13-52 newly diagnosed as in the first episode of Anorexia Nervosa Restricting Type, with a BMI below 18.7. The control group consisted of 10 clinically healthy women aged 21 to 52 years with a BMI from 23 to 25. Two types of orexigrams were found. The first was characterized by a low profile with negligible ultradian variability, in which the HS circadian rhythm (CR) was still detectable, but the power spectrum (PS) was composed of unusual ultradian components associated with a very diminished amplitude for the circadian harmonics. The second was characterized by an almost regular profile, in which the ultradian variability was clearly detectable, the CR regularly fluctuated, and the PS was almost regularly composed. These findings indicate that anorectic patients (AP) can be recognized by their orexigram as "hyporectic", or "eurectic". Therefore, the term "anorexia" seems to be appropriate for AP who exhibit the first type of orexigram (anorectic aphagia nervosa), whereas the second identifying those who could be defined as suffering from "eurectic aphagia nervosa".
Activity Cycles↗
Daily hunger sensation and body composition: I. Their relationships in clinically healthy subjects.
The human hunger sensation (HS) is a perceptive signal characterized by day-night variability (DNV). This pattern was investigated with respect to its relations with the body compartments in 22 clinically healthy subjects (CHS, 11 males and 11 females, mean age: 24 +/- 2.5 years, mean BMI: 21 +/- 1.7). The DNV was investigated by means of conventional descriptive statistics and the single cosinor method (SCM). Both procedures were applied to the orexigram, i.e., the 24-h profile of the orectic stimulus (OS) provided by each subject, who self-rated his/her HS (from 1 to 10 hunger units) every half hour. Body composition was investigated by Bioelectrical Impedance Analysis (BIA) on the day when the orexigrams were compiled. It was found that the daily HS level correlates positively with the Free Fat Body Mass (FFBM) and negatively with the Fat Body Mass (FBM). These opposite relations indicate that HS is stimulated by the needs of the FFBM, and inhibited by expansion of the FBM, and provide further evidence of the existence of an "adipostat" anorectic mechanism.
Adult↗
[The concept of "preclinical arterial hypertension" - in light of non-invasive, ambulatory blood pressure monitoring].
In clinical medicine it is possible to find subjects who show initial signs of hypertensive damage being normotensive at the "casual" sphygmomanometry. In order to verify whether or not these subjects are "true normotensives", it was applied the noninvasive ambulatory monitoring of blood pressure (BP). Five studies were performed: I. Normotensives with initial hypertensive retinopathy; II. normotensives with initial hypertensive cardiohypertrophy; III. Normotensives with initial hypertensive cardiohypertrophy of the transplanted heart; IV. Normotensive pregnant women with altered uterine blood flow; V. Normotensive pregnant women with intrauterine growth retardation. From all the studies, it was possible to derive that the subjects were all true normotensive. However, they were characterized by BP values on average higher than those of their controls, but below the reference limits given by WHO. Because of the relative elevation of BP, it was possible to argue that there exists a BP regimen which is potentially dangerous for the target organs, even though there is no evidence of manifest arterial hypertension. Such a hemodynamic condition causing hypertensive cardiovascular damage was defined "arterial pre-hypertension".
Blood Flow Velocity↗
A new mechanism of NK cell cytotoxicity activation: the CD40-CD40 ligand interaction.
NK recognition is regulated by a delicate balance between positive signals initiating their effector functions, and inhibitory signals preventing them from proceeding to cytolysis. Knowledge of the molecules responsible for positive signaling in NK cells is currently limited. We demonstrate that IL-2-activated human NK cells can express CD40 ligand (CD40L) and that recognition of CD40 on target cells can provide an activation pathway for such human NK cells. CD40-transfected P815 cells were killed by NK cell lines expressing CD40L, clones and PBL-derived NK cells cultured for 18 h in the presence of IL-2, but not by CD40L-negative fresh NK cells. Cross-linking of CD40L on IL-2-activated NK cells induced redirected cytolysis of CD40-negative but Fc receptor-expressing P815 cells. The sensitivity of human TAP-deficient T2 cells could be blocked by anti-CD40 antibodies as well as by reconstitution of TAP/MHC class I expression, indicating that the CD40-dependent pathway for NK activation can be downregulated, at least in part, by MHC class I molecules on the target cells. NK cell recognition of CD40 may be important in immunoregulation as well as in immune responses against B cell malignancies.
CD3 Complex↗
Growth of the parvovirus minute virus of mice MVMp3 in EL4 lymphocytes is restricted after cell entry and before viral DNA amplification: cell-specific differences in virus uncoating in vitro.
Two murine parvoviruses with genomic sequences differing only in 33 nucleotides (8 amino acids) in the region coding for the capsid proteins show different host cell specificities: MVMi grows in EL4 T lymphocytes and MVMp3 grows in A9 fibroblasts. In this study we compared the courses of infections with these two viruses in EL4 cells in order to investigate at which step(s) the infection process of MVMp3 is interrupted. The two viruses bound equally well to EL4 cells, and similar amounts of MVMi and MVMp3 input virion DNA appeared in the nuclear fractions of EL4 cells 1 h after infection. However, double-stranded replicative-form (RF) DNA of the two viruses appeared at different times, at 10 h postinfection with MVMi and at 24 h postinfection with MVMp3. The amount of MVMp3 RF DNA detected at 24 h was very small because it was produced only in a tiny subset of the population of EL4 cells that proved to be permissive for MVMp3. Replication of double-stranded viral DNA in EL4 cells was measured after transfection of purified RF DNA, cloned viral DNA, and cloned viral DNA with a mutation preventing synthesis of the capsid proteins. In each of these cases, DNA replication was comparable for MVMi and MVMp3. Production of virus particles also appeared to be similar after transfection of the two types of RF DNA into EL4 cells. Conversion of incoming 32P-labeled single-stranded MVM DNA to 32P-labeled double-stranded RF DNA was detected only after RF DNA amplification, indicating that few molecules serve as templates for viral DNA amplification. We showed that extracts of EL4 cells contain a factor which can destabilize MVMi virions but not MVMp3 by testing the sensitivity of viral DNA to DNase and by CsCl gradient analyses of viral particles. We therefore conclude that the MVMp3 life cycle is arrested after the transport of virions to the nucleus and prior to the replication of RF DNA, most likely at the stage of viral decapsidation.
Animals↗
[Who are the "non-dippers": an insight from the ambulatory monitoring of arterial pressure in heart transplant patients].
This study was performed in order to define who are the "non-dippers", knowing that their present definition does not imply any explanation about the mechanisms. The investigation was performed on 34 heart transplanted patients, 28 males (mean age 52 +/- 11 years) and 6 women (mean age 35 +/- 14 years), knowing that the "non-dippers" were described as the hypertensives who are devoid of the expected nocturnal fall in blood pressure (BP). The "non-dipping" phenomenon was investigated by exploring the BP 24-h pattern via ambulatory non-invasive BP monitoring, and by applying the rhythmometric analysis for quantifying the BP circadian rhythm. The study provided evidence that the "non-dippers" can be found among the hypertensives as well as the normotensives, suggesting that high BP is not a necessary condition for the "non-dipping" phenomenon, and vice versa. Both the normotensive and hypertensive "non-dippers" were seen to show stereotypic changes in BP circadian rhythm. There are normotensive and hypertensive "non-dippers" with or without the BP circadian rhythm. The "rhythmic non-dippers" show a BP circadian rhythm which is inverted in phase or demodulated in amplitude. The "non-dippers" are, thus, a heterogeneous category.
Adult↗
The role of CD4-Lck in T-cell receptor antagonism: evidence for negative signaling.
Small changes in the complex between a peptide and a molecule of the major histocompatibility complex generate ligands able to partially activate (partial agonist) or even inhibit (antagonist) T-cell functions. T-cell receptor engagement of antagonist complex results in a partial zeta chain phosphorylation without activation of the associated ZAP-70 kinase. Herein we show that, despite a strong inhibition of both inositol phospholipid hydrolysis and extracellular increasing antagonist concentrations increased the activity of the CD4-Lck kinase. Addition of anti-CD4 antibody to culture medium prevented inhibitory effects induced by antagonist ligand. We propose that CD4-Lck activation triggered by antagonist complexes may act in a dominant negative mode, thus overriding stimulatory signals coming from agonist ligand. These findings identify a new T-cell signaling profile that may explain the ability of some T-cell receptor variant ligands to inhibit specific biological activities or trigger alternative activation programs.
Amino Acid Sequence↗
Natural killer clones recognize specific soluble HLA class I molecules.
Enhancement of major histocompatibility complex (MHC) class I expression leads to protection from natural killer (NK) cell recognition in several systems. MHC class I gene products are released from the cell surface and can be found in sera as soluble forms. To investigate the possible immunoregulatory role of soluble HLA (sHLA) in NK cell-target recognition, several sHLA antigens were studied for their ability to induce NK cell cytotoxicity modulation. NK cell-target recognition was inhibited by the addition of sHLA during the cytotoxicity assay. Our results indicate that sHLA molecules can down-regulate NK killing at the effector level. Moreover, different NK clones are able to specifically recognize different sHLA antigens. Kp43 molecules seem to be involved in the NK recognition of sHLA-B7.
Antigens, CD↗
Satellited 4q identified in amniotic fluid cells.
Extra material was identified on the distal long arm of a chromosome 4 in an amniotic fluid specimen sampled at 16.6 weeks of gestational age. There was no visible loss of material from chromosome 4, and no evidence for a balanced rearrangement. The primary counseling issue in this case was advanced maternal age. Ultrasound findings were normal, and family history was unremarkable. The identical 4qs chromosome was observed in cells from a paternal peripheral blood specimen and appeared to be an unbalanced rearrangement. This extra material was NOR positive in lymphocytes from the father, but was negative in the fetal amniocytes. Father's relatives were studied to verify the familial origin of this anomaly. In situ hybridization with both exon and intron sequences of ribosomal DNA demonstrated that ribosomal DNA is present at the terminus of the 4qs chromosome in the fetus, father, and paternal grandmother. This satellited 4q might have been derived from a translocation event that resulted in very little or no loss from the 4q and no specific phenotype. This derivative chromosome 4 has been inherited through at least 3 generations of phenotypically normal individuals.
Amniotic Fluid↗