Showing papers by "University of Milan published in 1994"
TL;DR: The access matrix model is reviewed and different approaches to implementing the access matrix in practical systems are described, followed with a discussion of access control policies commonly found in current systems, and a brief consideration ofAccess control administration.
Abstract: Access control constrains what a user can do directly, as well as what programs executing on behalf of the users are allowed to do. In this way access control seeks to prevent activity that could lead to a breach of security. This article explains access control and its relationship to other security services such as authentication, auditing, and administration. It then reviews the access matrix model and describes different approaches to implementing the access matrix in practical systems, and follows with a discussion of access control policies commonly found in current systems, and a brief consideration of access control administration. >
1,432 citations
1,113 citations
TL;DR: This review proposes a new way of defining receptors for nucleotides, based on agonist potency order, transduction mechanisms and molecular structure, that will give a more ordered and logical approach to accommodating new findings.
1,101 citations
TL;DR: Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.
Abstract: BACKGROUND The powers of the low-frequency (LF) and high-frequency (HF) oscillations characterizing heart rate variability (HRV) appear to reflect, in their reciprocal relationship, changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions. However, no adequate information is available on the quantitative resolution of this methodology. METHODS AND RESULTS We studied 22 healthy volunteers (median age, 46.5 years) who were subjected after a rest period to a series of passive head-up tilt steps randomly chosen from the following angles: 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 90 degrees. From the continuous ECG, after appropriate analog-to-digital conversion, a personal computer was used to compute, with an autoregressive methodology, time and frequency domain indexes of RR interval variability. Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF. Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency (VLF), LF, and HF components. The tilt angle was correlated to both LF and HF (expressed in normalized units [nu]) and to the LF-to-HF ratio (r = .78, -.72, and .68; respectively). Lower levels of correlation were found with HF (in ms2) and RR interval. No correlation was present between tilt angle and variance, VLF, or LF (in ms2). Individual analysis confirmed that the use of nu provided the greatest consistency of results. CONCLUSIONS Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.
1,057 citations
TL;DR: Brain activity was mapped in normal subjects during passive obser-vation of the movements of an 'alien' hand and while imagining grasping objects with their own hand to support the notion that motor learning during observation of movements and mental practice involves rehearsal of neural pathways related to cognitive stages of motor control.
Abstract: Brain activity was mapped in normal subjects during passive observation of the movements of an 'alien' hand and while imagining grasping objects with their own hand. None of the tasks required actual movement. Shifting from one mental task to the other greatly changed the pattern of brain activation. During observation of hand movements, activation was mainly found in visual cortical areas, but also in subcortical areas involved in motor behaviour, such as the basal ganglia and the cerebellum. During motor imagery, cortical and subcortical areas related to motor preparation and programming were strongly activated. These data support the notion that motor learning during observation of movements and mental practice involves rehearsal of neural pathways related to cognitive stages of motor control.
955 citations
TL;DR: In this paper, the authors evaluated the impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS in a randomized controlled clinical trial.
Abstract: The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.
822 citations
TL;DR: A model of activation-induced, cytokine-modulated, programmed cell death as a major factor in the pathogenesis of HIV infection and AIDS is presented.
710 citations
TL;DR: The therapeutic efficacy of interferon alfa-2a in HCV-associated cryoglobulinemia is closely related to its antiviral activity, thus supporting the idea that HCV infection may be a cause of this disease.
Abstract: Background Essential mixed cryoglobulinemia is frequently associated with hepatitis C virus (HCV) infection. A beneficial effect of interferon alfa therapy has been reported, but we do not know whether the antiviral activity of the drug affects the clinical and biochemical manifestations of disease. Methods In a prospective randomized, controlled trial, we studied 53 patients with HCV-associated type II cryoglobulinemia. A group of 27 patients received recombinant interferon alfa-2a thrice weekly at a dose of 1.5 million units for a week and then 3 million units thrice weekly for the following 23 weeks. The 26 control patients did not receive anything apart from previously prescribed treatments. All patients were then followed for an additional 24 to 48 weeks. Results Interferon was usually well tolerated, but it was permanently discontinued in two patients because of atrial fibrillation and depression. Two of the 26 patients in the control group were lost to follow-up. After the treatment period, serum H...
554 citations
TL;DR: Important new information has been generated by coupling the analysis of heart rate variability (HRV) to the concept of sympatho-vagal balance, which explains part of the variability of RR interval.
Abstract: Even at rest the RR interval changes continuously around its mean value. Neural mechanisms account for part of this variability. Conventionally the interplay between sympathetic and vagal modulation of sinus node pacemaker activity is believed to be reciprocal-with increased activity in one system being accompanied by decreased activity in the other. Important new information has been generated by coupling the analysis of heart rate variability (HRV) to the concept of sympatho-vagal balance.'
497 citations
TL;DR: Data suggest that free radicals inhibit glutamate uptake primarily by long-lasting oxidation of protein sulfhydryl (SH) groups, and chemical modifiers of free SH groups, such as p-chloromercuribenzoate and N-ethylmaleimide, also induce uptake inhibition.
Abstract: Formation of reactive oxygen species and disfunction of the excitatory amino acid (EAA) system are thought to be key events in the development of neuronal injury in several acute and long-term neurodegenerative diseases. Recent evidence suggests that the two phenomena may be interdependent. The present study is aimed at exploring possible molecular mechanisms underlying oxygen radical-EAA interaction. Exposure of cortical astrocytic cultures to either xanthine + xanthine oxidase (X/XO), a free radical-generating system, or hydrogen peroxide (H2O2) results in a marked decrease of high-affinity glutamate transport. Within 10 min of X/XO application, uptake falls to approximately 60% of its control value. In parallel no detectable release of lactate dehydrogenase occurs. X/XO effect is abolished in the presence of a mixture of scavenger enzymes (superoxide dismutase+catalase) or by the disulfide-reducing agents glutathione and dithiothreitol (DTT), but not by lipophilic antioxidants or ascorbate. The time course of inhibition shows an almost linear decline of glutamate transport during cell exposure to free radicals, while upon their inactivation the decline stops but established inhibition persists for at least 1 hr. In this situation, application of DTT significantly restores transport function. These data suggest that free radicals inhibit glutamate uptake primarily by long-lasting oxidation of protein sulfhydryl (SH) groups. Chemical modifiers of free SH groups, such as p-chloromercuribenzoate and N-ethylmaleimide, also induce uptake inhibition. Na+/K+ ATPase is a known target of oxygen radicals and may be involved in glutamate uptake inhibition. Indeed, ouabain, a blocker of the pump, reduces uptake in astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
476 citations
TL;DR: The analysis of the genomic organization and expression of these genes in response to light shows that PAL and StSy genes belong to large multigene families, while the others are present in one to four copies per haploid genome.
Abstract: Genes involved in flavonoid and stilbene biosynthesis were isolated from grape (Vitis vinifera L.). Clones coding for phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin dioxygenase (LDOX) and UDP glucose:flavonoid 3-O-glucosyl transferase (UFGT), were isolated by screening a cDNA library, obtained from mRNA from seedlings grown in light for 48 h using snapdragon (Antirrhinum majus) and maize heterologous probes. A cDNA clone coding for stilbene synthase (StSy) was isolated by probing the library with a specific oligonucleotide. These clones were sequenced and when the putative products were compared to the published amino acid sequence for corresponding enzymes, the percentages of similarity ranged from 65% (UFGT) to 90% (CHS and PAL). The analysis of the genomic organization and expression of these genes in response to light shows that PAL and StSy genes belong to large multigene families, while the others are present in one to four copies per haploid genome. The steady-state level of mRNAs encoded by the flavonoid biosynthetic genes as determined in young seedlings is coordinately induced by light, except for PAL and StSy, which appear to be constitutively expressed.
TL;DR: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.
Abstract: BACKGROUND The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.
TL;DR: QT dispersion is a useful clinical tool to predict efficacy of antiadrenergic therapy in patients with long QT syndrome, and is significantly reduced by the surgical denervation to values similar to that of the responders to beta-blockade.
Abstract: BACKGROUNDQT interval dispersion, measured as interlead variability of QT, is a marker of dispersion of ventricular repolarization and, hence, of cardiac electrical instability. We tested the hypothesis that dispersion of ventricular repolarization may be differently affected by interventions destined to provide complete or incomplete protection against malignant arrhythmias in patients with long QT syndrome (LQTS). Twenty-eight patients affected by the Romano Ward form of LQTS entered the study and were divided into three groups: LQTS patients before institution of therapy, patients who did respond to beta-blocker therapy, and patients who continued to have syncope and cardiac arrest despite beta-blockade and who underwent left cardiac sympathetic denervation. A group of 15 healthy volunteers served as control subjects.METHODS AND RESULTSDispersion of QT and QTc were calculated using two indexes: the difference between the longest and the shortest value measured in each of the 12 ECG leads (QTmax-QTmin, ...
TL;DR: In this paper, the authors obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation.
Abstract: We obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at zero cm H2O end-expiratory pressure. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no. 1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density x height. The total volume of the basal CT section was 49 +/- 2.5 ml x m-2 (mean +/- SE) in control subjects and 43 +/- 2.3 ml x m-2 in patients with ARDS (p = not significant [NS]). The tissue volume, however, was 16.7 +/- 0.8 ml x m-2 in control subjects and 31.6 +/- 1.7 ml x m-2 in patients with ARDS (p < 0.01). The g/t ratio in level 1 averaged 4.7 +/- 0.5 in control subjects and 1.2 +/- 0.2 in patients with ARDS (p < 0.01), and this ratio decreased exponentially from level 1 to level 10, both in controls and patients with ARDS. The Kd constant of the exponential decrease was 13.9 +/- 1.3 cm in control subjects and 7.8 +/- 0.8 cm in patients with ARDS (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Journal Article•
TL;DR: In this paper, the authors obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation.
Abstract: We obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at zero cm H 2 O end-expiratory pressure. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no.1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density×height
TL;DR: A novel formulation for tight binding total energy calculations and tight binding molecular dynamics, which scales linearily with the size of the system, which is naturally parallelizable and permits us to perform molecular dynamics simulations of systems of unprecedented size.
Abstract: A novel formulation for tight binding total energy calculations and tight binding molecular dynamics, which scales linearily with the size of the system, is presented. The linear complexity allows us to treat systems of very large size and the algorithm is already faster than the best implementation of classical diagonalization for systems of 64 atoms. In addition, it is naturally parallelizable and it permits us therefore to perform molecular dynamics simulations of systems of unprecedented size. Finite electronic temperatures can also be taken into account. We illustrate this method by investigating structural and dynamical properties of solid and liquid carbon at different densities.
TL;DR: The field evolution is dominated by slippage effects in both cases, and shows the presence of superradiant spikes.
Abstract: We study the time structure, the frequency composition, and the shot to shot fluctuations of the radiation emitted by a free-electron laser starting from shot noise in the electron beam longitudinal distribution, taking into account slippage and finite bunch length effects. We find a very different behavior when the bunch length, ${\mathit{scrl}}_{\mathit{b}}$ is much longer thatn the cooperation length, ${\mathit{scrl}}_{\mathit{c}}$, or of the order of a few ${\mathit{scrl}}_{\mathit{c}}$. The field evolution is dominated by slippage effects in both cases, and shows the presence of superradiant spikes.
TL;DR: Late ARDS showed lower respiratory compliance, higher dead space, higher Paco2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS, and the late stages may be described as restrictive lung disease with superimposed emphysemalike lesions.
Abstract: Objective. —To assess the clinical consequences of duration of adult respiratory distress syndrome (ARDS) on lung structure and function. Design. —Retrospective analysis. Setting. —A university hospital referral center for extracorporeal support. Patients. —A total of 84 patients with severe ARDS (Murray score >2.5) recruited from 48 intensive care units (1979 to 1992), who suffered ARDS and underwent mechanical ventilation for up to 1 week (37 patients with early ARDS), between 1 and 2 weeks (24 patients with intermediate ARDS), or more than 2 weeks (23 patients with late ARDS) and subsequently underwent extracorporeal support. Main Outcome Measures. —Before beginning extracorporeal support, we measured gas exchange, pulmonary mechanics, hemodynamics, oxygen transport and delivery, incidence of barotrauma (presence of one or more thoracic tubes for pneumothorax drainage), and organ dysfunctions. In a subgroup of 16 patients, we studied lung structure by computed tomographic scan, scoring the densities and quantifying the emphysemalike lesions (bullae). Results. —Late ARDS showed lower respiratory compliance, higher dead space, higher Paco2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS (P Conclusions. —The lung structure and function changes markedly with ARDS duration, and the late stages may be described as restrictive lung disease with superimposed emphysemalike lesions. Presence of pneumothorax affects survival and appears to be related to the lung structural changes occurring with time. (JAMA. 1994;271:1772-1779)
TL;DR: It is submitted that right-handers differ in the degree of their RH specialization in processing faces and that in only a minority of them is it so marked that it cannot be compensated for by the healthy left hemisphere.
Journal Article•
TL;DR: The results suggest that the placement of implants protruding 3 to 4 mm from the top of resorbed bone surfaces may result in vertical bone regeneration to thetop of the implant cylinder and that the regenerated bone is able to osseointegrate pure titanium implants.
Abstract: The purpose of this study was to evaluate: (1) the surgical protocol, effectiveness, and reliability for vertical ridge augmentation using a new titanium-reinforced membrane and osseointegrated implants; and (2) the histologic characteristics of the interface between a pure titanium implant and newly regenerated human bone. Five patients received 15 conical Branemark-type implants in six different surgical sites requiring vertical augmentation. The implants protruded 4 to 7 mm from the bone crest. Pure titanium miniscrews (1.3 x 10 mm) were positioned distally to the implants, protruding 3 to 4 mm from the bone level. The implants and the miniscrews were covered with a titanium-reinforced membrane, and the flaps were sutured. Membranes were removed at the stage 2 surgery after 9 months of healing. Measurements of biopsy specimens showed a gain in bone height from 3 to 4 mm. Histologic examination showed that all retrieved miniscrews were in direct contact with bone. Histomorphometric analysis of bone contact gave a mean value of 42.5 +/- 3.6% for five of the six examined miniscrews. The results suggest that the placement of implants protruding 3 to 4 mm from the top of resorbed bone surfaces may result in vertical bone regeneration to the top of the implant cylinder and that the regenerated bone is able to osseointegrate pure titanium implants.
TL;DR: The results of the MAL, favoring chemotherapy, are in line with those of a MAP recently published and have to be considered in the light of their actual clinical relevance and of the balance between quality of life, toxicity, and costs of chemotherapy and best supportive care.
TL;DR: Evidence is looked at that quantal release of neurotransmitter from clear synaptic vesicles may occur by a similar 'kiss-and-run' mechanism to that of exocytosis.
TL;DR: In this article, it was shown that for any mapping ψe, analytic and e-close to the identity, there exists an analytic autonomous Hamiltonian system, He such that its time-one mapping ΦHe differs from ψ e by a quantity exponentially small in 1/e. This result is applied to the problem of numerical integration of Hamiltonian systems by symplectic algorithms.
Abstract: We reconsider the problem of the Hamiltonian interpolation of symplectic mappings. Following Moser's scheme, we prove that for any mapping ψe, analytic and e-close to the identity, there exists an analytic autonomous Hamiltonian system, He such that its time-one mapping ΦHe differs from ψe by a quantity exponentially small in 1/e. This result is applied, in particular, to the problem of numerical integration of Hamiltonian systems by symplectic algorithms; it turns out that, when using an analytic symplectic algorithm of orders to integrate a Hamiltonian systemK, one actually follows “exactly,” namely within the computer roundoff error, the trajectories of the interpolating Hamiltonian He, or equivalently of the rescaled Hamiltonian Ke=e-1He, which differs fromK, but turns out to be e5 close to it. Special attention is devoted to numerical integration for scattering problems.
TL;DR: It is shown here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats.
Abstract: The Milan hypertensive strain of rats (MHS) develops a genetic form of renal hypertension that, when compared to its normotensive control (MNS), shows renal dysfunction similar to that of a subset of human patients with primary hypertension. MHS and MNS were shown to be homozygous by multilocus minisatellite analysis and monolocus microsatellite markers. We show here that one point mutation in each of two genes coding for the membrane skeleton protein adducin is associated with blood pressure in the Milan strain of rats. Adducin is a heterodimer formed by alpha and beta subunits that promotes the assembly of actin with spectrin. MHS and MNS differ, respectively, by the amino acids Y and F at position 316 of the alpha subunit. In the beta-adducin locus, MHS is always homozygous for R at position 529 while in MNS either R or Q occurs in that position. The R/Q heterozygotes showed lower blood pressure than any of the homozygotes. In vitro phosphorylation studies suggest that both of these amino acid substitutions occur within protein kinase recognition sites. Analysis of an F2 generation demonstrated that Y alleles segregated with a significant increment in blood pressure. This effect is modulated by the presence of the R allele of the beta subunit. Taken together, these findings strongly support a role for adducin polymorphisms in causing variation of blood pressure in the Milan strain of rats.
TL;DR: There appears to be a therapeutic window for fluoxetine, and the pharmacokinetics of this drug are not affected by either obesity or renal impairment, which makes this drug particularly suitable for use in elderly patients with depression.
Abstract: Fluoxetine is well absorbed after oral intake, is highly protein bound, and has a large volume of distribution. The elimination half-life of fluoxetine is about 1 to 4 days, while that of its metabolite norfluoxetine ranges from 7 to 15 days. Fluoxetine has a nonlinear pharmacokinetic profile. Therefore, the drug should be used with caution in patients with a reduced metabolic capability (i.e. hepatic dysfunction). In contrast with its effect on the pharmacokinetics of other antidepressants, age does not affect fluoxetine pharmacokinetics. This finding together with the better tolerability profile of fluoxetine (compared with tricyclic antidepressants) makes this drug particularly suitable for use in elderly patients with depression. Furthermore, the pharmacokinetics of fluoxetine are not affected by either obesity or renal impairment. On the basis of results of plasma concentration-clinical response relationship studies, there appears to be a therapeutic window for fluoxetine. Concentrations of fluoxetine plus norfluoxetine above 500 µg/L appear to be associated with a poorer clinical response than lower concentrations. Fluoxetine interacts with some other drugs. Concomitant administration of fluoxetine increased the blood concentrations of antipsychotics or antidepressants. The interactions between fluoxetine and lithium, tryptophan and monoamine oxidase inhibitors, in particular, are potentially serious, and can lead to the ‘serotonergic syndrome’. This is because of synergistic pharmacodynamic effects and the influence of fluoxetine on the bioavailability of these compounds.
TL;DR: The results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype, which is relevant to ‘risk assessment’ procedures.
Abstract: THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined1,2. Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust3,4. We have determined levels of DNA adducts in bladder cells and of 4-aminobipheny7l–haemo-globin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine–cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine–cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine–cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to ‘risk assessment’ procedures.
TL;DR: In patients with congestive heart failure the set point of fluid balance is altered in spite of oral furosemide therapy; supplemental intravenous furoSemide does not shift the setpoint, at least not when combined with ACE inhibition.
TL;DR: The frequent occurrence of anti–neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.
Abstract: We studied the frequency and clinical correlates of different IgM specificities in 75 patients with neuropathy associated with IgM monoclonal gammopathy. Patients were tested for IgM reactivity with the myelin-associated glycoprotein, PO, neurofilaments, and tubulin by immunoblot; with GM1, asialo-GM1, GM2, GD1a, GD1b, sulfatide, and chondroitin sulfate C by enzyme-linked immunosorbent assay; and with brain and nerve glycolipids by overlay highperformance thin-layer chromatography. Forty-two patients (56%) had high titers of IgM antibodies to MAG; 4 (5%), to sulfatide (1 also to myelin-associated glycoprotein); 4 (5%), to the 200-kd neurofilament (2 also to myelin-associated protein); and 1 each, to GD1b and chondroitin sulfate C. No reactivity was found in 26 patients (35%). More patients with anti–myelin-associated glycoprotein IgM (62%) than with unknown IgM reactivity (31%) had a predominantly sensory neuropathy (p < 0.025). Nerve conduction findings were consistent with a demyelinating neuropathy in 77% of patients reactive to myelin-associated glycoprotein and 24% with unknown reactivity (p < 0.0001) and the mean conduction velocity of peroneal nerve was lower in the former group (22.9 m/sec) than in the latter group (39.6 m/sec) (p < 0.000001). Patients with anti–sulfatide IgM had a sensorimotor neuropathy with morphological evidence of demyelination while anti–neurofilament IgM was not associated with homogeneous findings. Patients with anti–GD1b or anti–chondroitin sulfate C IgM had a predominantly motor impairment. The frequent occurrence of anti–neural IgM antibodies in neuropathy associated with IgM gammopathy, and their frequent, though not constant association with similar neuropathy features, support their possible pathogenetic role in the neuropathy.
TL;DR: The findings indicate that in psoriasis the altered ceramide distribution can be linked specifically to the defect in keratinocyte differentiation; the defects in skin barrier function may be attributed largely or in part to ceramide 1 reduction.
Abstract: Background and Design: In psoriasis the formation of the cornified layer is deranged and water flux is reportedly increased. We investigated three different forms of psoriasis: transepidermal water loss was measured on uninvolved skin and psoriatic plaques; lipids from plaques were extracted; and ceramide distribution in scale vs normal stratum corneum was compared. Moreover, the lipid biochemical results were compared with transepidermal water loss rates in the same lesions. To assess potential alteration in ceramide distribution, lipids from both psoriatic scale and normal stratum corneum were extracted by the Bligh-Dyer method, separated on high performance thin layer chromatography plates, and quantified by computerized densitometry. Water flux was measured as transepidermal water loss using an evaporimeter; results between uninvolved and involved psoriatic skin and age-matched control skin were statistically evaluated. Results: In comparison with normal stratum corneum, psoriatic plaque ceramides showed a different distribution; in particular, ceramide 1 was significantly decreased. The increased transepidermal water loss values of psoriatic plaques vs control skin and between Psoriatic involved vs uninvolved skin were significant. Conclusion: Our findings indicate that in psoriasis the altered ceramide distribution can be linked specifically to the defect in keratinocyte differentiation; the defect in skin barrier function may be attributed largely or in part to ceramide 1 reduction. (Arch Dermatol. 1994;130:452-456)
TL;DR: Two approaches are described to determine whether the factor VIII preparations were the cause of HAV infection in the patients with hemophilia: the results of a casecontrol study carried out in the Italian cohort to determine the source of Hav infection and theresults of sequence analyses of H AV cDNA amplified by reverse transcriptase and polymerase chain reactions from specific lots of factor VIII and from serum samples of recipients in whom hepatitis A developed.
Abstract: Objective: To determine whether an outbreak of hepatitis A virus (HAV) infection that occurred in 52 patients with hemophilia in Italy was acquired through infusion of contaminated factor VIII or t...