Showing papers by "University of Milan published in 1989"

An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis

Abstract: A specific assay has been developed for a blood-borne non-A, non-B hepatitis (NANBH) virus in which a polypeptide synthesized in recombinant yeast clones of the hepatitis C virus (HCV) is used to capture circulating viral antibodies. HCV antibodies were detected in six of seven human sera that were shown previously to transmit NANBH to chimpanzees. Assays of ten blood transfusions in the United States that resulted in chronic NANBH revealed that there was at least one positive blood donor in nine of these cases and that all ten recipients seroconverted during their illnesses. About 80 percent of chronic, post-transfusion NANBH (PT-NANBH) patients from Italy and Japan had circulating HCV antibody; a much lower frequency (15 percent) was observed in acute, resolving infections. In addition, 58 percent of NANBH patients from the United States with no identifiable source of parenteral exposure to the virus were also positive for HCV antibody. These data indicate that HCV is a major cause of NANBH throughout the world.

GTPase inhibiting mutations activate the α chain of G s and stimulate adenylyl cyclase in human pituitary tumours

Abstract: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s) The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras

Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing.

Abstract: The accuracy of blood pressure values obtained by continuous noninvasive finger blood pressure recording via the FINAPRES device was evaluated by comparison with simultaneous intraarterial monitoring both at rest and during performance of tests known to induce fast and often marked changes in blood pressure. The comparison was performed in 24 normotensive or essential hypertensive subjects. The average discrepancy between finger and intra-arterial blood pressure recorded over a 30-minute rest period was 6.5 +/- 2.6 mm Hg and 5.4 +/- 2.9 mm Hg for systolic and diastolic blood pressure, respectively; a close between-method correspondence was also demonstrated by linear regression analysis. The beat-to-beat changes in finger systolic and diastolic blood pressure were on average similar to those measured intra-arterially during tests that induced a pressor or depressor response (hand-grip, cold pressor test, diving test, Valsalva maneuver, intravenous injections of phenylephrine and trinitroglycerine) as well as during tests that caused vasomotor changes without major variations in blood pressure (application of lower body negative pressure, passive leg raising). The average between-method discrepancy in the evaluation of blood pressure changes was never greater than 4.3 and 2.0 mm Hg for systolic and diastolic blood pressure, respectively; the corresponding standard deviations ranged between 4.6 and 1.6 mm Hg. Beat-to-beat computer analysis of blood pressure variability over the 30-minute rest period provided standard deviations almost identical when calculated by separate consideration of intra-arterial and finger blood pressure tracings (3.7 and 3.8 mm Hg, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis and design of optimum-amplitude nine-switch direct AC-AC converters

Abstract: The maximum input-output transformer ratio, or output voltage ability, of direct AC-AC pulse-width-modulated converters is explored. An intrinsic limit, independent of the control algorithm, is found. A suitable novel converter control algorithm is discussed which achieves such maximum output amplitude ability and displays some interesting features. Finally, the opportunity to implement AC-AC converter control with the use of feedback techniques is considered, and a feedback-based control algorithm for the converter is proposed. >

Selective recruitment of high-threshold human motor units during voluntary isotonic lengthening of active muscles.

Abstract: 1. We have investigated the possibility that voluntary muscle lengthening contractions can be performed by selective recruitment of fast-twitch motor units, accompanied by derecruitment of slow-twitch motor units. 2. The behaviour of motor units in soleus, gastrocnemius lateralis and gastrocnemius medialis muscles was studied during (a) controlled isotonic plantar flexion against a constant load (shortening contraction, S), maintained plantar flexion, or dorsal flexion resisting the load and gradually yielding to it (lengthening contraction, L), (b) isometric increasing or decreasing plantar torque accomplished by graded contraction or relaxation of the triceps surae muscles, (c) isometric or isotonic ballistic contractions, and (d) periodic, quasi-sinusoidal isotonic contractions at different velocities. The above tasks were performed under visual control of foot position, without activation of antagonist muscles. The motor units discharging during foot rotation were grouped on the basis of the phase(s) during which they were active as S, S + L and L. The units were also characterized according to both the level of isometric ramp plantar torque at which they were first recruited and the amplitude of their action potential. 3. S units were never active during dorsal flexion; some of them were active during the sustained contraction between plantar and dorsal flexion. Most S + L units were active also during the maintenance phase and were slowly derecruited during lengthening; their behaviour during foot rotations was similar to that during isometric contractions or relaxations. L units were never active during either plantar or maintained flexion, but discharged during lengthening contraction in a given range of rotation velocities; the velocity of lengthening consistently influenced the firing frequency of these units. Such dependence on velocity was not observed in S + L units. 4. A correlation was found between the amplitude of the action potential and the threshold torque of recruitment among all the units. In addition, the amplitudes of both the action potential and the threshold torque were higher in the case of L units than in the case of S and S + L units. Most L units could be voluntarily recruited only in the case of ballistic isometric or isotonic contraction. 5. Occasionally, L units were directly activated by electrical stimulation of motor fibres and their conduction velocity was in the higher range for alpha-axons. In contrast, nerve stimulation could induce a reflex activation of S and S + L units.(ABSTRACT TRUNCATED AT 400 WORDS)

Geometry of type ii superstrings and the moduli of superconformal field theories

Abstract: We study general properties of the low-energy effective theory for 4D type II superstrings obtained by the compactification on an abstract (2,2) superconformal system. This is the basic step towards the construction of their moduli space. We give an explicit and general algorithm to convert the effective Lagrangian for the type IIA into that of type IIB superstring defined by the same (2,2) superconformal system (and vice versa). This map converts Kahler manifolds into quaternionic ones (and quaternionic into Kahlerian ones) and has a deep geometrical meaning. The relationship with the theory of normal quaternionic manifolds (and algebras), as well as with Jordan algebras, is outlined. It turns out that only a restricted class of quarternionic geometries is allowed in the string case. We derive a general and explicit formula for the (fully nonlinear) couplings of the vector-multiplets (IIA case) in terms of the basic three-point functions of the underlying superconformal theory. A number of illustrative e...

A case-control study of gastric cancer and diet in Italy.

Abstract: A case-control study was conducted in high- and low-risk areas of Italy to evaluate reasons for the striking geographic variation in gastric cancer (GC) mortality within the country. Personal interviews with 1,016 histologically confirmed GC cases and 1,159 population controls of similar age and sex revealed that the patients were more often of lower social class and resident in rural areas and more frequently reported a familial history of gastric (but not other) cancer. After adjusting for these effects, case-control differences were found for several dietary variables, assessed by asking about the usual frequency of consumption of 146 food items and beverages. A significant trend of increasing GC risk was found with increasing consumption of traditional soups, meat, salted/dried fish and a combination of cold cuts and seasoned cheeses. The habit of adding salt and the preference for salty foods were associated with elevated GC risk, while more frequently storing foods in the refrigerator, the availability of a freezer and use of frozen foods lowered risk. Reduced GC risk were associated with increasing intake of raw vegetables, fresh fruit and citrus fruits. Lowered risk was also related to consumption of spices, olive oil and garlic. Neither cigarette smoking nor alcoholic beverage drinking were significantly related to GC risk. The case-control differences tended to be consistent across geographic areas, despite marked regional variations in intake levels of certain foods. The high-risk areas tended to show higher consumption of food associated with elevated risk (traditional soups, cold cuts) and lower consumption of foods associated with reduced risks (raw vegetables, citrus fruits, garlic). Our findings indicate that dietary factors contribute to the regional variation of stomach cancer occurrence in Italy, and offer clues for further etiologic and prevention research.

Inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in cerebellar Purkinje neurons.

Abstract: INOSITOL 1,4,5-trisphosphate (InsP3) mediates the effects of several neurotransmitters, hormones and growth factors by mobilizing Ca2+ from a vesicular, non-mitochondrial intracellular store1 Many studies have indirectly suggested the endoplasmic reticulum (ER) to be the site of InsP3 action2–6, though some have implicated the plasma membrane7,8 or a newly described smooth surfaced structure, termed the calciosome9 Using antibodies directed against a purified InsP3-receptor glycoprotein10, of relative molecular mass 260,000, in electron microscope immunocytochemical studies of rat cerebellar Purkinje cells, we have now localized the InsP3 receptor to ER, including portions of the rough endoplasmic reticulum, a population of smooth-membrane-bound organelles (smooth ER), a portion of subplas-malemmal cisternae and the nuclear membrane, but not to mitochondria or the cell membrane These results suggest that in cerebellar Purkinje cells, InsP3-induced intracellular calcium release is not the property of a single organelle, but is effected by specialized portions of both rough and smooth ER, and possibly by other smooth surfaced structures The present findings are the first immunocytochemical demonstration of an InsP3 receptor within a cell

Monokine production by microglial cell clones.

Abstract: Cytokines have been suggested to act as intermediates between the immune and the central nervous system, but little is known about the type of cells synthesizing them in the brain. We have immortalized with oncogenic retroviruses primary brain cell cultures from mouse embryos and have generated clones of microglial cells that have been characterized. Three of the clones studied produce interleukin 1 (IL 1); IL 6 and tumor necrosis factor-alpha as assessed by biological assays and by Northern blot analysis. Our data raise the question on the role of these cytokines in the brain and suggest that early resident microglial cells might play an important role in development processes and in the adult brain.

Respiratory mechanics in anesthetized paralyzed humans: effects of flow, volume, and time.

Abstract: The effects of inspiratory flow rate and inflation volume on the resistive properties of the total respiratory system were investigated in 16 anesthetized paralyzed humans by using the technique of rapid airway occlusion during constant flow inflation. This allowed measurement of the intrinsic resistance (Rmin,rs) and of the effective additional resistance (delta Rrs) as the result of viscoelastic pressure dissipations within the pulmonary and chest wall tissues. We observed that 1) at fixed inflation volume, Rmin,rs increased linearly with increasing flow although delta Rrs decreased according to an exponential function; 2) at fixed inflation flow, Rmin,rs decreased with increasing inflation volume although there was a concomitant increase in delta Rrs. This behavior could be explained in terms of a spring-and-dashpot model incorporating 1) the standard resistance and elastance and 2) a spring-and-dashpot in parallel with standard elastance, reflecting the stress adaptation units within the thoracic tissues.

The effect of execution policies on the semantics and analysis of stochastic Petri nets

Abstract: Petri nets in which random delays are associated with atomic transitions are defined in a comprehensive framework that contains most of the models already proposed in the literature. To include generally distributed firing times into the model one must specify the way in which the next transition to fire is chosen, and how the model keeps track of its past history; this set of specifications is called an execution policy. A discussion is presented of the impact that different execution policies have on semantics of the mode, as well as the characteristics of the stochastic process associated with each of these policies. When the execution policy is completely specified by the transition with the minimum delay (race policy) and the firing distributions are of the phase type, an algorithm is provided that automatically converts the stochastic process into a continuous time homogeneous Markov chain. An execution policy based on the choice of the next transition to fire independently of the associated delay (preselection policy) is introduced, and its semantics is discussed together with possible implementation strategies. >

Spectral analysis of R-R and arterial pressure variabilities to assess sympatho-vagal interaction during mental stress in humans

Abstract: We tested the hypothesis that spectral analysis of the R-R interval and systolic arterial pressure variabilities allows assessment of the dynamic changes in neural control of the cardiovascular system in men undergoing mental stress testing. Mental arithmetic increased the low-frequency components of R-R and systolic arterial pressure, i.e. markers of sympathetic activity to the SA node and the vasculature, respectively; it also decreased the high frequency component of R-R variability, a marker of vagal activity. Spectral analysis of R-R and systolic arterial pressure variabilities may be used in the clinic to test the dynamic effects of mental stress on both sympathetic and vagal activities.

Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets.

Abstract: The role of LFA-1, a member of the integrin supergene family, in intercellular adhesion, including lymphocyte-endothelial cell (EC) binding, has been established We now demonstrate that differences in LFA-1 cell surface density are responsible for the variable adhesion efficiency of lymphocyte subsets to EC Electrophoretic analysis revealed multiple glycosylated isoforms of both alpha and beta subunits, largely as a result of different degrees of sialylation, with variable expression among different lymphocyte subsets Neuraminidase digestion before EC adhesion increased the binding efficiency of all lymphocyte subsets, although the relative increase in each subset was proportional to the initial LFA-1 sialic acid content LFA-1 cross-linking resulted in phosphoinositide hydrolysis and a rise in [Ca2+]i when using anti-alpha but not anti-beta subunit antibodies These findings indicate that the density of LFA-1 on lymphocyte subsets controls their adhesive properties, and that the LFA-1 alpha subunit has transmembrane signaling properties that may result in activation events after interaction with its natural ligands

Genetics of Angiosperm Pollen

Abstract: Publisher Summary The angiosperm life cycle consists of two alternating phases—a diploid, morphologically elaborate and conspicuous sporophyte, and a much reduced, haploid gametophyte. At least four phenomena in the ontogeny of pollen impinge on the genetic determination of pollen quality: Cytoplasmic interconnections, which establish developmental synchrony among meiocytes, callose envelopes, which isolate microspores from each other, tapetal deposits, which coat the pollen exine, and sporophytic inputs, which remain in the meiocyte cytoplasm. Some pollen characteristics are determined exclusively by the sporophyte, as is the case with the exine. Others, such as Ga factors, gametophytic self-incompatibility, and the presence of specific enzymes (alcohol dehydrogenase, P-galactosidase, are under gametophytic control. Pollen competition may be significant phenomenon in the evolution of crop species and also in the reduction of genetic load. Pollen competition may play a significant role in the adaptive capacities of the angiosperms, as this group possesses three characteristics, which enhance pollen tube competition. These are: Heavy stigmatic loads of pollen, the simultaneous arrival of many pollen grains on the stigma, and the requirement for extensive pollen tube growth. Finally, direct and indirect in vivo interactions between pollen grains and particularly pollen-pistil interactions need evaluation.

Comparison of nifedipine, propranolol and isosorbide dinitrate on angiographic progression and regression of coronary arterial narrowings in angina pectoris

Abstract: Calcium antagonists and beta blockers may retard or inhibit atherogenesis. This study investigated whether nifedipine or propranolol influences coronary atherosclerosis in humans. In selected patients with effort angina and proven coronary artery disease, the cineangiographic pattern after 2-year therapy with nifedipine (group 1, 39 patients), propranolol (group 2, 36 patients) or isosorbide dinitrate (group 3, 38 patients) was compared to that before treatment. The disease evolved to a different extent in the 3 groups. Patients with evidence of progression of old narrowings and appearance of new narrowings were significantly fewer in group 1 (31% and 10%) than in group 2 (53% and 34%) and group 3 (47% and 29%). The number of stenoses with evidence of progression was significantly smaller after nifedipine (14), and larger after propranolol (39) compared with group 3 (24). Thus, nifedipine seemed more protective than the other 2 drugs against coronary atherosclerosis. The coronary risk factors were normal in the nifedipine group and remained so with treatment, suggesting that they were dissociated from influences on atherosclerosis. The evolution, as judged by the number of narrowings with progression, appeared significantly (p less than 0.01) worse with propranolol than with isosorbide dinitrate. Propranolol caused unfavorable modifications of serum lipids; there was a 28% increase in total triglycerides and a 25% decrease in high density lipoprotein cholesterol at 12 months in group 2.

Anderson transition in a one-dimensional system with three incommensurate frequencies.

Abstract: We report results of numerical investigations of the quantum dynamics of a 1D system subject to a time-dependent perturbation with three incommensurate frequencies. These results demonstrate a transition from localized to extended states occurring at a critical value of the perturbation parameter. The dependence of the localization length and of the diffusion rate on this parameter near the critical point is analyzed and found to be in agreement with the predictions of renormalization-group theory.

Binding of von Willebrand factor to glycoproteins Ib and IIb/IIIa complex: affinity is related to multimeric size

Abstract: We have separated von Willebrand factor (vWF) multimers of different size into several fractions which were characterized by SDS-agarose gel electrophoresis and by measuring the ratio between ristocetin cofactor activity (Ricof) and von Willebrand antigen (vWF:Ag) content. The pooled fractions contained vWF with multimeric structures and Ricof similar to those in plasma. The pool was labelled with 125I and used for inhibition binding studies with individual fractions to calculate the dissociation constants (Kd values expressed in mol/l) of the individual fractions for ristocetin-dependent binding to GP Ib and thrombin-induced binding to GP IIb/IIIa. Direct binding studies of the 125I-vWF pool gave mean Kd values of 2.02 +/- 0.05 x 10(-8) for GP Ib and 1.15 +/- 0.02 x 10(-8) for the GP IIb/IIIa complex. Inhibition binding studies gave Kd mean values one third to one tenth as high for larger multimers and 3-10 times higher for smaller multimers, for both GP Ib and IIb/IIIa complex. Similar results were observed when binding studies were carried out in the presence of platelets from a patient with afibrinogenaemia. These data on binding correlated very well with ristocetin- and thrombin-induced aggregation of afibrinogenaemic platelets, since equal concentrations of the higher molecular weight forms gave significantly higher aggregation rates. Based on these results, we conclude that the affinity of the vWF molecule for its two platelet receptors is greater for the largest multimers.

Ten-year mortality study of the population involved in the Seveso incident in 1976.

Abstract: In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a populated area by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The area was subdivided into three zones (A, B, and R) having decreasing mean levels of TCDD soil contamination. This study examines the mortality between 1976 and 1986 among the subjects, aged 20-74 years, who were resident in the area since the accident (n = 556 in zone A, n = 3,920 in zone B, n = 26,227 in zone R). Subjects' exposure was classified by residence. A referent cohort of 167,391 subjects who lived in the immediate surroundings was concurrently examined. Vital status ascertainment was successful for over 99% of the subjects. Increased mortality from cardiovascular causes was found; incident-related stressors were considered more relevant to increased mortality than was TCDD exposure. Mortality from several cancers was elevated. The increases in biliary cancer (females), brain cancer, and lymphatic and hemopoietic neoplasms (particularly leukemia in males) did not appear to result from chance, confounding, or information/comparison bias. However, no definite patterns related to exposure classification were apparent. Merely suggestive increases in soft tissue tumors and melanoma were also noted. Liver and breast cancer mortality tended to be below expectations. Interpretation is hampered by the short observation period, small number of deaths from certain causes, and poor exposure definition. Further research is in progress.

Direct modulation of Aplysia S-K+ channels by a 12-lipoxygenase metabolite of arachidonic acid.

Abstract: Lipoxygenase metabolites of arachidonic acid have recently been shown to modulate the activity of ion channels in nerve and muscle cells. The mechanism of action of these metabolites is, however, unknown. In sensory neurons of Aplysia, the S-K- channel is under the dual modulatory control of 5-hydroxytryptamine (5-HT), which decreases the number of active S channels through cyclic AMP-dependent phosphorylation, and the neuropeptide FMRFamide, which increases the probability of S-channel opening through the 12-lipoxygenase metabolite 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Here we report that the increase in the probability of S-channel opening with FMRFamide is mimicked by application of 12-HPETE to cell-free membrane patches that lack ATP and GTP. Thus, 12-HPETE can act directly to modulate S-channel activity, independently of protein phosphorylation or dephosphorylation, G-protein activation or cyclic nucleotides.

Superradiance in the high-gain free-electron laser.

Abstract: In this paper we describe the effects of slippage on the single-pass high-gain free-electron laser (FEL) amplifier. We use a one-dimensional computational code to show the existence of two new dynamical regimes characterized by a dimensionless parameter {ital K}, which is a measure of the slippage in one gain length. We define the long-pulse limit to be when {ital K}{much lt}1 or the electron pulse length {ital L}{sub {ital e}} is much greater than a properly defined cooperation length'' {ital L}{sub {ital c}} ({ital L}{sub {ital e}}{much gt}L{sub c}). In this case we find that only the leading region of the propagating radiation pulse exhibits the usual steady-state behavior, with peak power proportional to {ital n}{sub {ital e}}{sup 4/3} (where {ital n}{sub {ital e}} is the electron-beam density). The trailing (slippage) region exhibits a spiking behavior with peak intensities reaching many times the saturated intensity predicted by steady-state theory. We define the short-pulse regime to be when {ital K}{approx gt}1 ({ital L}{sub {ital e}}{approx lt}L{sub c}). In this regime the peak power emitted by the electrons does not scale as {ital n}{sub {ital e}}{sup 4/3}, as predicted by steady-state theory, but scales as {ital n}{sub {ital e}}{sup 2}, which ismore » typical of superradiant behavior. Furthermore, energy is extracted from the electrons in a continuous way, with no steady-state synchrotron oscillatory-type behavior.« less