Showing papers by "University of Brescia published in 1998"
TL;DR: The pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis is reviewed and it is proposed that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints.
Abstract: During the last decade, the GH axis has become the compelling focus of remarkably active and broad-ranging basic and clinical research. Molecular and genetic models, the discovery of human GHRH and its receptor, the cloning of the GHRP receptor, and the clinical availability of recombinant GH and IGF-I have allowed surprisingly rapid advances in our knowledge of the neuroregulation of the GH-IGF-I axis in many pathophysiological contexts. The complexity of the GHRH/somatostatin-GH-IGF-I axis thus commends itself to more formalized modeling (154, 155), since the multivalent feedback-control activities are difficult to assimilate fully on an intuitive scale. Understanding the dynamic neuroendocrine mechanisms that direct the pulsatile secretion of this fundamental growth-promoting and metabolic hormone remains a critical goal, the realization of which is challenged by the exponentially accumulating matrix of experimental and clinical data in this arena. To the above end, we review here the pathophysiology of the GHRH somatostatin-GH-IGF-I feedback axis consisting of corresponding key neurotransmitters, neuromodulators, and metabolic effectors, and their cloned receptors and signaling pathways. We propose that this system is best viewed as a multivalent feedback network that is exquisitely sensitive to an array of neuroregulators and environmental stressors and genetic restraints. Feedback and feedforward mechanisms acting within the intact somatotropic axis mediate homeostatic control throughout the human lifetime and are disrupted in disease. Novel effectors of the GH axis, such as GHRPs, also offer promise as investigative probes and possible therapeutic agents. Further understanding of the mechanisms of GH neuroregulation will likely allow development of progressively more specific molecular and clinical tools for the diagnosis and treatment of various conditions in which GH secretion is regulated abnormally. Thus, we predict that unexpected and enriching insights in the domain of the neuroendocrine pathophysiology of the GH axis are likely be achieved in the succeeding decades of basic and clinical research.
1,189 citations
TL;DR: It is shown that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tail, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region.
Abstract: In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.
901 citations
TL;DR: A dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.
Abstract: The human homologue of Drosophila Toll (hToll) is a recently cloned receptor of the interleukin 1 receptor (IL-1R) superfamily, and has been implicated in the activation of adaptive immunity. Signaling by hToll is shown to occur through sequential recruitment of the adapter molecule MyD88 and the IL-1R–associated kinase. Tumor necrosis factor receptor–activated factor 6 (TRAF6) and the nuclear factor κB (NF-κB)–inducing kinase (NIK) are both involved in subsequent steps of NF-κB activation. Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways.
611 citations
TL;DR: The interaction between HBV and HCV infections was negative according to the multiplicative model, providing epidemiological evidence both of an independent effect and of interference between the 2 viruses in the carcinogenic process.
Abstract: The aim of the study was to assess whether co-infection by hepatitis-B virus (HBV) and hepatitis-C virus (HCV) is associated with a higher risk of developing hepatocellular carcinoma (HCC) than each infection alone. A meta-analysis of data published up to June 1997 was performed. HBsAg and anti-HCV antibodies or HCV RNA (anti-HCV/HCV RNA) were considered as serological markers of current HBV and HCV infection respectively. A total of 32 case-control studies were suitable for a quantitative overview. The summary odds ratios (OR) were 13.7 for HBsAg positivity and 11.5 for anti-HCV/HCV RNA positivity. The OR for anti-HCV was lower among studies using second- or third-generation anti-HCV or HCV RNA (OR, 8.2) with respect to studies with first-generation anti-HCV test (OR, 19.1). When combining data from the studies with second- or third-generation anti-HCV or HCV RNA, the OR for HBsAg positivity and anti-HCV/HCV RNA negativity was 22.5 (95% confidence interval (CI), 19.5-26.0), the OR for anti-HCV/HCV RNA positivity and HBsAg negativity was 17.3 (95% CI, 13.9-21.6), and the OR for both markers positivity was 165 (95% CI: 81.2-374, based on 191 cases and 8 controls exposed). A synergism was found between HBV and HCV infections, the OR for co-infection being greater than the sum and lower than the product of those for each infection alone. The interaction was therefore negative according to the multiplicative model, providing epidemiological evidence both of an independent effect and of interference between the 2 viruses in the carcinogenic process.
538 citations
TL;DR: Cells cultured in the presence of IL‐10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin to specific T cell lines with much less efficiency than control DC.
Abstract: Human monocytes cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-13 for 7 days differentiate into cells with the morphology and function of dendritic cells (DC). We have investigated the effect of IL-10 on this differentiation pathway. In the presence of IL-10 cells did not develop DC morphology, did not express CD1a and had lower levels of MHC class II. IL-10 promoted the differentiation of large cells with the morphology, cytochemistry and membrane phenotype of macrophages, including staining for nonspecific esterase and high levels of CD14, CD16 and CD68. The effect of IL-10 was dose dependent and was best appreciated when the cytokine was added at the initiation of the culture, as addition on day 3 was less inhibitory. When added to already differentiated DC on day 6, IL-10 caused only a modest reduction of MHC class II and CD1a expression, and no acquisition of the macrophage markers CD14, CD16 and CD68. Prolonged incubation up to 5 days with IL-10 did not induce a shift of differentiated DC to macrophages. On the other hand, the macrophages obtained by culturing for 7 days with GM-CSF+IL-13+IL-10 did not shift to DC upon removal of IL-10 for up to 3 days. Thus, the effect of IL-10 on monocyte differentiation, occurs only at the precursor level and confers an irreversible phenotype. From a functional point of view, cells cultured in the presence of IL-10 were poor stimulators of allogeneic cord blood T cells in mixed lymphocyte reaction (MLR) and presented tetanus toxin (TT) to specific T cell lines with much less efficiency than control DC. In contrast, IL-10-cultured DC showed 7 times greater endocytosis of FITC-dextran. This increased endocytosis was mostly mediated via the mannose receptor, as demonstrated by blocking with unlabeled mannose. In conclusion, IL-10 inhibits DC differentiation from monocytes and, in a substantial proportion of the cells, promotes the differentiation to mature macrophages. Intriguingly, IL-10 inhibits antigen presentation while it stimulates endocytic activity.
499 citations
TL;DR: It is reported here that patients with Omenn syndrome, a severe immunodeficiency characterized by the presence of activated, anergic, oligoclonal T cells, hypereosinophilia, and high IgE levels, bear missense mutations in either the Rag-1 or Rag-2 genes that result in partial activity of the two proteins.
422 citations
Journal Article•
TL;DR: In this paper, the authors showed that the immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis, where tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis.
Abstract: Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.
343 citations
TL;DR: The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation, and the proposed index is obtained without an a-priori definition of the pattern length.
Abstract: A new method for measuring the regularity of a process over short data sequences is reported. This method is based on the definition of a new function (the corrected conditional entropy) and on the extraction of its minimum. This value is taken as an index in the information domain quantifying the regularity of the process. The corrected conditional entropy is designed to decrease in relation to the regularity of the process (like other estimates of the entropy rate), but it is able to increase when no robust statistic can be performed as a result of a limited amount of available samples. As a consequence of the minimisation procedure, the proposed index is obtained without an a-priori definition of the pattern length (i.e. of the embedding dimension of the reconstructed phase space). The method is validated on simulations and applied to beat- to-beat sequences of the sympathetic discharge obtained from decerebrate artificially ventilated cats. At control, regular, both quasiperiodic and periodic (locked to ventilation) dynamics are observed. During the sympathetic activation induced by inferior vena cava occlusion, the presence of phase-locked patterns and the increase in regularity of the sympathetic discharge evidence an augmented coupling between the sympathetic discharge and ventilation. The reduction of complexity of the neural control obtained by spinalization decreases the regularity in the sympathetic outflow, thus pointing to a weaker coupling between the sympathetic discharge and ventilation.
266 citations
TL;DR: In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions.
Abstract: BackgroundIt is unclear whether the carotid intima–media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principa
264 citations
TL;DR: The results show that day–night blood pressure changes and the classification of patients into dippers and non-dippers are poorly reproducible over time and provides the first prospective evidence that treatment-induced changes in day-time blood pressure difference are not related to treatment- induced regression of left ventricular mass index.
Abstract: ObjectiveTo assess whether modifications in the night-time blood pressure fall caused by antihypertensive treatment predict the regression of end-organ damage of hypertension.MethodsThe analysis was performed in patients with essential hypertension and echocardiographically detected left ventricular
252 citations
TL;DR: An amplification loop of polarized Th2 responses based on differential regulation of MDC production by IL-4 and IL-13 versus IFN-gamma and on the selectivity of this chemokine for polarized Th1 cells are delineated.
TL;DR: IL-6 activates PBMCs to secrete MCP-1, a CC chemokine pivotal for monocyte recruitment in tissue and organs in which important inflammatory events occur, and IL-6 induction of M CP-1 was partially inhibited by hydrocortisone in U1 cells.
TL;DR: The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough: peak ratio.
Abstract: ObjectiveTo introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough: peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index in
TL;DR: Exposure to concentrations of inorganic lead in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology, and a possible modest effect on endocrine profile was shown.
Abstract: OBJECTIVE: To critically review the literature on male reproductive toxicity of lead in animals and humans. METHODS: A systematic literature search identified a total of 32 experimental studies in animals and 22 epidemiological studies, one case report on humans and five review articles or documents. The studies were evaluated by paying attention mainly to sample size, study design, exposure, and dose characterisation, analytical method standardisation, and quality assurance. RESULTS: Several studies on rats and other rodents indicated that blood lead concentrations > 30-40 micrograms/dl were associated with impairment of spermatogenesis and reduced concentrations of androgens. However, other animal studies, mainly about histopathological, spermatozoal, and hormonal end points, indicated that certain species and strains were quite resistant to the reproductive toxicity of lead and that different testicular lead concentrations could account for these differences. The human studies focused mainly on semen quality, endocrine function, and birth rates in occupationally exposed subjects, and showed that exposure to concentrations of inorganic lead > 40 micrograms/dl in blood impaired male reproductive function by reducing sperm count, volume, and density, or changing sperm motility and morphology. No relevant effects were detected on endocrine profile. CONCLUSION: Several factors make it difficult to extrapolate the animal data to the human situation. The difficulties are mainly due to differences between species in reproductive end points and to the level of exposure. Concentrations of blood lead > 40 micrograms/dl seemed to be associated with a decrease in sperm count, volume, motility, and morphological alterations and a possible modest effect on endocrine profile. Dose-response relation, in particular at a threshold level, is poorly understood, and site, mode, or mechanism of action are unknown. Also, the effects were not always the same or associated in the same on sperm count and concentration. Some methodological issues and indications for future studies are discussed.
TL;DR: Object and action naming was significantly greater in FTD than in AD patients, independent of the severity of dementia or of overall language impairment, and this finding is compatible with the hypothesis that the frontal lobe plays a crucial role in action naming.
Abstract: To assess noun and verb processing in different dementia types, we tested object and action naming in three groups of subjects: probable Alzheimer's disease (AD) with mild to moderate dementia; age- and education-matched normal subjects; and a group of frontotemporal dementia (FTD) patients. AD and FTD patients were impaired in naming compared with control subjects; action naming was more severely impaired. However, the discrepancy between object and action naming was significantly greater in FTD than in AD patients, independent of the severity of dementia or of overall language impairment. The latter finding is compatible with the hypothesis that the frontal lobe plays a crucial role in action naming. A relatively selective impairment in action naming might be a characteristic neuropsychological feature of FTD.
Journal Article•
TL;DR: An association of HLA class I antigen and TAP down-regulation with tumor progression in breast carcinoma is demonstrated, suggesting that loss of Hla and/or TAP may represent an escape from the host's immune pressure or may reflect the accumulation of abnormalities associated with neoplastic progression.
Abstract: Five specimens of normal mammary tissue and 53 primary breast carcinoma lesions were tested for expression of HLA antigens and components of the antigen-processing machinery by immunohistochemical staining. The expression of transporter associated with antigen processing (TAP) 1, TAP2, and HLA class I antigens in breast carcinoma lesions was significantly associated with tumor grading. Like normal mammary tissue, the 16 low-grade (G1) breast carcinoma lesions showed strong staining for TAP1, TAP2, and HLA class I antigens. In contrast, only 12 (32%) of 37 high-grade (G2 and G3) breast carcinoma lesions displayed the normal staining pattern. In 14 (38%) of 37 high-grade lesions, HLA class I antigen down-regulation was observed without loss of low molecular mass polypeptide and/or TAP staining. Congruent down-regulation of HLA class I antigen and TAP1 or TAP2 was found in 8 (22%) of 37 high-grade lesions. Complete loss of HLA class I antigens, TAP1, and TAP2 was observed in 3 (8%) of 37 high-grade lesions. No lesion was negative for TAP1 and/or TAP2 staining while positive for HLA class I antigen staining. These data demonstrate an association of HLA class I antigen and TAP down-regulation with tumor progression in breast carcinoma. This association suggests that loss of HLA and/or TAP may represent an escape from the host's immune pressure or may reflect the accumulation of abnormalities associated with neoplastic progression. This accumulation of defects in antigen processing and presentation may in turn be responsible for reduced recognition of malignant cells by putative clinically relevant tumor-specific T cells.
TL;DR: In vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 is demonstrated and the effects of PTEC infection to explain the pathogenesis of tubular damage in vivo are described and the results indicate that PTEC express HIV-specific receptor and coreceptors and sustain virus replication.
Abstract: HIV-infected patients suffer several renal syndromes, which can progress rapidly from renal insufficiency to end-stage renal disease. Histologically, HIV-induced nephropathy is characterized by prominent tubulopathy with apoptosis of tubular cells. Clinical and experimental evidence suggests that renal injury may be directly related to virus infection. Although HIV-1 is a polytropic and not solely lymphotropic pathogen, the susceptibility of renal cells to HIV-1 remains to be determined. This paper demonstrates in vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 and describes the effects of PTEC infection to explain the pathogenesis of tubular damage in vivo. The results indicate that PTEC express HIV-specific receptor and coreceptors and sustain virus replication. We observed that HIV-1 infection causes the death of tubular cells by triggering an apoptotic pathway involving caspase activation. Fas upregulation but not Fas ligand expression was found in the infected PTEC. However, after HIV-1 infection, tubular cells became susceptible to apoptosis induced through Fas stimulation. Caspase inhibition prevented the death of the infected PTEC in spite of persistent viral replication. These findings may explain the prominent histopathology of HIV-associated nephropathy and demonstrate that the apoptosis of nonlymphoid cells can be directly induced by HIV-1.
Journal Article•
TL;DR: Monocytes derived from four patients with molecularly defined typical WAS have a severely impaired migration in response to FMLP and to the chemokines monocyte chemoattractantprotein-1 (MCP-1) and macrophage inflammatory protein-1alpha compared with normal donors.
Abstract: Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by trombocytopenia, eczema, and progressive decline of the immune function. In addition, lymphocytes and platelets from WAS patients have morphologic abnormalities. Since chemokines may induce morphologic changes and migration of leukocytes, we investigated the monocyte response to chemoattractants in cells from WAS patients with an identified mutation in the WAS protein gene. Here, we report that monocytes derived from four patients with molecularly defined typical WAS have a severely impaired migration in response to FMLP and to the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha compared with normal donors. Conversely, neither MCP-1 binding to monocytes nor induction of the respiratory burst by MCP-1 and FMLP is significantly different between WAS patients and normal donors. Within a few minutes of stimulation, monocytes respond to chemokines with increased expression of adhesion molecules and with morphologic changes such as cell polarization. Although up-regulation of CD11b/CD18 expression following stimulation with FMLP or MCP-1 is preserved in WAS patients, cell polarization is dramatically decreased. Staining of F-actin by FITC-phalloidin in monocytes stimulated with chemoattractants shows F-actin to have a rounded shape in WAS patients, as opposed to the polymorphic distribution of F-actin in the polarized monocytes from healthy donors. These results suggest that WAS protein is involved in the monocyte response to the chemokines MCP-1 and macrophage inflammatory protein-1alpha.
TL;DR: The results suggest that reasoning about syllogisms engages distinct brain mechanisms, depending on the intention to evaluate them deductively versus probabilistically.
23 Feb 1998
TL;DR: This paper presents innovative encoding techniques suitable for minimizing the switching activity of system-level address buses, and targets the reduction of the average number of bus line transitions per clock cycle.
Abstract: The power dissipated by system-level buses is the largest contribution to the global power of complex VLSI circuits. Therefore, the minimization of the switching activity at the I/O interfaces can provide significant savings on the overall power budget. This paper presents innovative encoding techniques suitable for minimizing the switching activity of system-level address buses. In particular, the schemes illustrated here target the reduction of the average number of bus line transitions per clock cycle. Experimental results, conducted on address streams generated by a real microprocessor, have demonstrated the effectiveness of the proposed methods.
TL;DR: A significant proportion of DC was able to migrate across the endothelial basement membrane and, subsequently, across the vascular endothelial barrier (reverse transmigration) and the adhesion molecules and chemoattractants characterized herein are likely to underlie the complex trafficking of DC in vivo.
TL;DR: The results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.
Abstract: The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.
Proceedings Article•
01 Jul 1998TL;DR: Preliminary results on the effectiveness of adding computed state constraints and predicate domains to the specification of problems for SAT-based planners such as SATPLAN or MEDIC are shown.
Abstract: We describe some new preprocessing techniques that enable faster domain-independent planning. The first set of techniques is aimed at inferring state constraints from the structure of planning operators and the initial state. Our methods consist of generating hypothetical state constraints by inspection of operator effects and preconditions, and checking each hypothesis against all operators and the initial conditions. Another technique extracts (supersets of) predicate domains from sets of ground literals obtained by Graphplan-like forward propagation from the initial state. Our various techniques are implemented in a package called DISCOPLAN. We show preliminary results on the effectiveness of adding computed state constraints and predicate domains to the specification of problems for SAT-based planners such as SATPLAN or MEDIC. The results suggest that large speedups in planning can be obtained by such automated methods, potentially obviating the need for adding hand-coded state constraints.
TL;DR: The serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly, which should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations.
Abstract: In this study we assessed the safety, efficacy and cost-effectiveness of the use of triple dose gadolinium-DTPA (Gd) in serial monthly brain MRI of patients with multiple sclerosis, such as could be selected for clinical trials. The number of enhancing lesions, the number of new enhancing lesions and the number of active scans were used to evaluate the sensitivity of the contrast-enhanced MRI to disease activity. The dose of Gd, and the effect of introducing a delay between the contrast injection and the scan were both appraised. Every 4 weeks for 3 months, and in two separate sessions, scans were obtained from 40 patients with relapsing-remitting or secondary progressive multiple sclerosis, 5 min (early) and 20 min (delayed) after a standard dose (0.1 mmol/kg) or triple dose (0.3 mmol/kg) Gd injection. There were 435 enhancing lesions (242 of which were new) on the early standard dose scans, 479 (263 new) on the delayed standard dose, 772 (365 new) on the early triple dose and 827 (404 new) on the delayed triple dose. There were 109 scans revealing active disease on the early standard dose scans, 112 on the delayed standard dose, 119 on the early triple dose and 120 on the delayed triple dose. Statistical simulations indicated that the sample sizes needed for both cross-over and parallel-group trials with similar powers are lower if serial monthly triple dose MRI is used. No side-effects were reported and no significant changes in blood test parameters were found throughout the study. This study shows that the serial use of triple dose Gd is safe, and that it increases the sensitivity of serial monthly enhanced MRI in detecting multiple sclerosis activity significantly. Its use should enable preliminary trials of experimental therapies for multiple sclerosis to be conducted in small patient populations, over a short period of time.
TL;DR: In this paper, the authors report about preparation and characterization of thin films of MoO3 as a material for gas-sensing applications, carried out by electron microscopy and X-ray diffraction techniques.
Abstract: The authors report about preparation and characterization of thin films of MoO3 as a material for gas-sensing applications. Structural investigation of the films is carried out by electron microscopy and X-ray diffraction techniques. The sensing behavior of the MoO3 films was tested to NO2, showing capability to detect a few ppm of NO2 with considerably short response time.
TL;DR: The pattern of CCR8 mRNA expression and the functional effects exerted by its ligand suggest that the triggering of this receptor may regulate multiple functions including activation, migration and proliferation of lymphoid cells.
Abstract: Section of Pathology and Immunology, Department of Biotechnology, University of Brescia,Brescia, ItalyChemokines are key molecules in directing leukocyte migration toward sites of inflamma-tion. We have previously cloned a putative CC chemokine receptor gene, TER1, whoseexpression is restricted to lymphoid tissues and cell lines. Recently, this receptor has beenshown to signal in response to the human CC chemokine I-309 and thus it has beenrenamed CCR8 according to the current nomenclature. In the present study, we report theidentification of the CC chemokines thymus and activation-regulated cytokine (TARC) andmacrophage inflammatory protein-1 (MIP-1 ) as CCR8 ligands, as they induce chemotaxisin CCR8 Jurkat stable transfectants. Furthermore, we have generated a polyclonal antise-rum that is able to recognize the CCR8 molecule in transfectant lysates. The pattern of CCR8mRNA expression and the functional effects exerted by its ligand suggest that the triggeringof this receptor may regulate multiple functions including activation, migration and prolifera-tion of lymphoid cells.
TL;DR: The data demonstrate that correction of metabolic acidosis improves serum albumin concentrations in HD patients, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins.
Abstract: BACKGROUND Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. STUDY DESIGN In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. RESULTS Serum bicarbonate levels and arterial pH increased respectively from 19.3 +/- 0.6 mmol/l to 24.4 +/- 1.2 mmol/l (P < 0.0001) and 7.34 +/- 0.03 to 7.40 +/- 0.02 (P < 0.0001). Serum albumin increased from 34.9 +/- 2.1 g/l to 37.9 +/- 2.9 g/l (P < 0.01), while PCRn decreased from 1.11 +/- 0.17 g/kg/day to 1.03 +/- 0.17 g/kg/day (P < 0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. CONCLUSIONS Our data demonstrate that correction of metabolic acidosis improves serum albumin concentrations in HD patients. The correction of acidosis induces a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.
TL;DR: The results indicate that deltamethrin, in the presence of metabolic activation (+ S9mix), is able to induce DNA damage as revealed by the increasing tail moment values observed with increasing doses.
TL;DR: The results of this investigation demonstrate that vertical laminar airflow hoods, when incorrectly used, might represent a source of contamination and that higher risk may depend on lack of educational programmes and observance of preventive guidelines.
Abstract: Twenty four workers (10 involved in the preparation and 14 in administration) exposed to cyclophosphamide (CP) and ifosfamide (IF) in two Italian hospitals were monitored. The extent of exposure was assessed by the analysis of air samples, wipe samples, pads and gloves. Urinary excretion at the beginning and at the end of the work shift was also measured by liquid-liquid extraction and analysis by high performance liquid chromatography/tandem mass spectrometry. Three out of 24 air samples were positive for CP or IF. In wipe samples, CP concentrations ranging from < 0.001 to 82.4 micrograms/dm2 in Hospital A (32 samples) and from 0.2 to 383.3 micrograms/dm2 in Hospital B (17 samples), were found. IF concentrations varied from < 0.001 to 90.9 micrograms/dm2 in Hospital A and from 0.01 to 141.5 micrograms/dm2 in Hospital B. Pads (from 11 to 13 for each operator) were contaminated with CP and IF especially on arms, legs and chest. The use of a plastic-backed liner on the working tray in the laminar flow hoods was demonstrated to compromise the containment properties of the hood. Urine samples were positive for CP in 50% of the workers (range: 0.1-2.1 micrograms/L), whereas IF was detected in 2 subjects only (range: 0.1-0.8 microgram/L). The results of this investigation demonstrate that vertical laminar airflow hoods, when incorrectly used, might represent a source of contamination and that higher risk may depend on lack of educational programmes and observance of preventive guidelines.
TL;DR: In this article, a linearized heat flux law involving positive instantaneous conductivity is matched with the energy balance, to generate an autonomous semilinear system subject to initial history and Dirichlet boundary conditions.
Abstract: This paper is devoted to existence, uniqueness and asymptotic behavior, as time tends to infinity, of the solutions of an integro-partial differential equation arising from the theory of heat conduction with memory, in presence of a temperature-dependent heat supply. A linearized heat flux law involving positive instantaneous conductivity is matched with the energy balance, to generate an autonomous semilinear system subject to initial history and Dirichlet boundary conditions. Existence and uniqueness of solution is provided. Moreover, under proper assumptions on the heat flux memory kernel, the existence of absorbing sets in suitable function spaces is achieved.