Reduced carrier cooling and thermalization in semiconductor quantum wires.
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Biomedical subjects
Publications and source records attributed to F Rossi.
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The disulphide bridged heptapeptide Boc-Cys-Val-Pro-Pro-Phe-Phe-Cys-OMe has been synthesized by classical solution methods. An ion binding study showed the peptide's ability to complex calcium ions with definite stoichiometry. The solution conformation of the peptide in its free and calcium-complexed form has been investigated by CD and nmr. The model structure derived from nmr data has been energy minimized and the resulting structure investigated by molecular dynamics simulation in water. The structure of the equimolar peptide/Ca2+ complex in acetonitrile at room temperature shows the presence of two transannular hydrogen bonds, with the formation of two ring structures of the C10 (type VIa) and C14 type. One peptide unit (Pro-Pro) is cis, all others are trans.
We report that an antibody engineered to express three Arg-Gly-Asp (RGD) repeats in the third complementarity-determining region of the heavy chain (antigenized antibody) efficiently inhibits the lysis of human erythroleukemia K-562 cells by natural killer (NK) cells. Synthetic peptides containing RGD did not inhibit. Inhibition was specific for the (RGD)3-containing loop and required simultaneous occupancy of the Fc receptor (CD16) on effector cells. The antigenized antibody inhibited other forms of cytotoxicity mediated by NK cells but not cytotoxicity mediated by major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL). A three-dimensional model of the engineered antibody loop shows the structure and physicochemical characteristics probably required for the ligand activity. The results indicate that an RGD motif is involved in the productive interaction between NK and target cells. Moreover, they show that peptide expression in the hypervariable loops of an antibody molecule is an efficient procedure for stabilizing oligopeptides within a limited spectrum of tertiary structures. This is a new approach towards imparting ligand properties to antibody molecules and can be used to study the biological function and specificity of short peptide motifs, including those involved in cell adhesion.
We have previously shown that in neutrophils classical transmembrane signaling consisting of increased [Ca2+]i and hydrolysis of phospholipids was not essential for phagocytosis mediated by more than one receptor (yeast-IgG, yeast-C3b/bi, yeast-Con A). This work deals with the role of this transmembrane signaling in phagocytosis of erythrocyte (E) IgG, which is mediated only by receptors for IgG (Fc gamma Rs). The ingestion of E-IgG was associated with an increase in [Ca2+]i and production of inositol phosphates, phosphatidic acid, diacylglycerol, and arachidonic acid, via activation of phospholipases C, D and A2. Related to the same number of particles ingested, the respiratory burst and the transmembrane signaling during phagocytosis of E-IgG were much smaller than during phagocytosis of yeast-IgG. In Ca(2+)-depleted neutrophils, where the increase in [Ca2+]i and hydrolysis of phospholipids were lacking, the phagocytosis of E-IgG was depressed by about 60%; the respiratory burst was also depressed due to the decrease of ingestion and of stimulation of NADPH oxidase by residual phagocytosis. Pertussis toxin (PT) did not inhibit the phagocytosis of E-IgG but depressed by about 40% the stimulation of lipidic transmembrane signaling and the respiratory burst in normal neutrophils. In Ca(2+)-depleted neutrophils the toxin was without effect on ingestion and respiratory burst. Staurosporine did not inhibit the ingestion of E-IgG in normal and Ca(2+)-depleted neutrophils but depressed by 30-40% the respiratory burst in normal and not in Ca(2+)-depleted neutrophils. Genistein, an inhibitor of tyrosine kinase, did not inhibit the ingestion of E-IgG but depressed by 30-40% the respiratory burst both in normal and Ca(2+)-depleted neutrophils. These results demonstrate the following findings in human neutrophils. (1) Contrary to the phagocytosis mediated by more than one receptor (yeast-IgG, yeast-Con A, yeast-C3b/bi), the transmembrane signaling involving increase in [Ca2+]i and hydrolysis of phospholipids plays a role in the phagocytosis and respiratory burst mediated by Fc gamma Rs alone. Thus, different signal transduction pathways can be involved in phagocytosis and associated respiratory burst depending on the receptor or combination of receptors activated. (2) Fc gamma Rs alone promote phagocytosis with two signaling pathways independent of and dependent on [Ca2+]i changes and phospholipid hydrolysis and insensitive to PT, staurosporine, and genistein. (3) The signaling pathways promoting phagocytosis triggered by Fc gamma Rs alone are in some way, or at some step, different from those that activate the respiratory burst.
Chronic alcoholic pancreatitis (CAP) is often complicated by the onset of diabetes mellitus. The aim of this study was to assess the residual beta cell function (evaluated by means of the glucagon test) and the mean disposal rate of insulin (with the insulin tolerance test) in 66 CAP patients with or without abnormalities of glucose metabolism and in 19 control subjects. On the basis of our data, we conclude that the glucose metabolism abnormalities in chronic pancreatitis occurs as a result not merely of impaired production of endogenous insulin, but also as result of a combination of the latter together with insulin resistance.
An altered autonomic balance is considered to be a pathogenetic factor in cluster headache syndrome, although there is varying data on sympathetic and/or parasympathetic activation during attacks and/or attack-free intervals. The aim of the present study was to evaluate the day/night pattern of heart rate during the active and remission phases of cluster headache. In addition, the relationship between heart rate changes and the site of pain was investigated to determine if an autonomic imbalance was related to the lateralization of pain. Thirty-nine patients (34 with primary episodic cluster headache and five with primary chronic cluster headache and 30 healthy controls underwent 24-h Holter ECG recording. Nine cluster headache patients were monitored during both phases of the disease. The data obtained confirmed the existence of a disordered chrono-organization in cluster headache (phase-shift of approximately 1 h of heart rate rhythm during the cluster period) together with a low heart rate variability and a higher occurrence of arrhythmias in cluster headache patients with right-sided pain. Differences were also observed in the cluster headache patients when headache free, excluding the pain itself as a reason for the abnormality. The chronobiological data point out a transient rhythmic dysfunction, while heart rate variability changes, mostly related either to the phase of the disease or to the site of pain, probably reflects a central, site-related, dysfunction of the autonomic nervous system in cluster headache.
The relationship between the interleukin-2 (IL-2) system and the humoral response against human immunodeficiency virus type-I (HIV-1) is important in understanding the immune reaction before the development of AIDS. Levels of IL-2 and soluble IL-2 receptor (sIL-2R) in serum and cerebrospinal fluid (CSF) samples from 31 asymptomatic HIV-1 seropositive individuals were measured and correlated with levels of anti-1 IgG and IgM antibodies. High IL-2 levels were detected in the CSF of 20 (65%) subjects, 18 (90%) of whom had evidence of intrathecal synthesis of HIV-1-specific IgM antibodies. Similarly, IgG antibodies were detected in 10 subjects who had elevated IL-2 levels in the CSF. Moreover, intrathecal levels of IL-2 and sIL-2R correlated with intrathecal synthesis of both IgG and IgM antibodies. Local release of IL-2 seems to play an important role in the initiation of the antibody response against HIV-1 in early stages of infection and may be utilised in devising effective therapeutic strategies.
In order to define the purinergic receptors subtype involved in the control of cardiovascular activity, the effects of intracerebroventricular (icv 3rd ventricle) or intravenous (i.v.) injection of purinergic agonists and antagonists were evaluated on arterial blood pressure and heart rate of anaesthetized normotensive adult male rats. Adenosine (Ado) an A1 and A2 purinergic receptors agonist, N6-cyclohexyladenosine (CHA), an A1 receptor agonist and 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), an A2 purinergic receptor agonist, were administered in rats by icv (0.01-0.05-0.1 microgram) and i.v. (0.1-0.5-1 microgram/kg) injections. The animals treated with adenosine were either pretreated with an A1 (8-cyclopenthyl-1,3-dimethylxanthine, CPT) an A2 (3,7dimethyl-1-propargylxanthine, DMPX) or an A1-A2 (aminophylline, APH) purinergic receptor antagonist by icv (0.05 microgram) or i.v. (0.5 microgram/kg) injected or not at all pretreated. Ado, CPCA and CHA produced a dose-dependent decrease in arterial blood pressure and heart rate. The effects of CHA were less marked than those caused by Ado and CPCA. The icv and i.v. pretreatment with aminophylline, CPT and DMPX inhibited arterial hypotension and bradycardia induced by Ado, CHA and CPCA. The inhibitor effects of aminophylline and DMPX were stronger than those caused by CPT. These results showed that in the cerebral areas near the 3rd ventricle the purinergic system plays an important role in the control of cardiovascular function. The involvement of A2 purinergic receptors after administration of adenosine or its analogs on central and peripheral cardiovascular activity was also confirmed.
The role of postsynaptic neurons in the maintenance of adult terminal axon arbours was investigated in the rat olivocerebellar system. The degeneration of Purkinje cells, the main target of olivary axons in the cerebellar cortex, was obtained by intraparenchymal application of kainate. The structural features of target-deprived climbing fibres, visualized by Phaseolus vulgaris leucoagglutinin tracing, were examined from two days to six months after the lesion. Following the degeneration of its Purkinje cell, the climbing fibre underwent remarkable regressive modifications involving the disappearance of most of the terminal arborization. Never the less, atrophic arbours still spanned through the molecular layer six months after the lesion. Morphometric evaluations showed that, one week after kainate application, total arbour length was already reduced to 52% of control, whereas the number of branches and of varicosities had both dropped around 40%. This retraction process progressed in the following stages to reach its maximum at about one month after the lesion, when total length was 30% of control and only 10% of branches and varicosities were still present. Only a slight tendency to a further decrease of the values could be detected at longer survival times. Branching pattern analysis revealed that such regressive phenomena mainly involved the distal compartment of the climbing fibres, the one made of fine varicose branchlets, while sparing the proximal thick branches. In addition, the whole process appeared to follow some rather strict guiding principles leading to an ordered branch retraction, from the periphery of the arbour inwards. Finally, in order to rule out the possibility that the observed changes could be due to a direct action of kainate on climbing fibres, we designed an alternative method of killing Purkinje cells by intraparenchymal injection of propidium iodide. The structural features of climbing fibres deprived of their target by such a procedure were very similar to those shown by arbours from time-matched kainate-lesioned animals at both qualitative and quantitative levels. Our results show that target deprivation induces remarkable structural modifications in the climbing fibre, leading to the retraction of most of the arbour. Never the less, the integrity of the Purkinje cell is not necessary for the maintenance of the whole arborization since its proximal compartment is maintained in the molecular layer for several months after target degeneration. It is proposed that the Purkinje cell, most likely by acting through a contact factor, directly controls the formation and the maintenance of the distal climbing fibre branches with their varicosities, which represent the presynaptic compartment of the axonal arbour.
This paper describes a system to record incisal and condylar movements. It consists of two Charge Coupled Device (CCD) cameras that detect the position of markers fixed to the face, real-time hardware to recognize the markers and software for three-dimensional reconstruction of condylar and mandibular movements. The subject sat upright in front of the cameras and was asked to perform jaw movements. The position of the markers was recorded and the coordinates were fed into the computer and converted to three-dimensional kinematic data by a mathematical algorithm implemented on an AT IBM personal computer. Dedicated software calculated the head movements and the mandibular movements separately and performed a three-dimensional mathematical reconstruction of the movements of the condylar points and the interincisive point, using the geometrical rules of a rigid body. This pilot study describes the pattern from opening, closing, protrusive, and lateral movements as obtained from healthy subjects with good dentition.
The contemporaneous employment of two or more drugs may present the risk of modifying the required therapeutic effect or producing adverse reactions. These interactions are of a pharmacokinetic and pharmacodynamic type. Teicoplanin is an antibiotic with a glycopeptide structure, produced by Actinoplanes teichomyceticus, active against both anaerobic and aerobic Gram-positive bacteria that are resistant to various chemotherapeutic drugs (beta-lactam and macrolide antibiotics, tetracyclines, co-trimoxazole). Then the aim of this work was to verify experimentally the possible pharmacological interactions between teicoplanin and oral hypoglycemic (phenformin and glibenclamide), or oral anticoagulant (warfarin) or bronchodilator (theophylline) drugs. Teicoplanin (3-15 mg/kg/die i.p. for 4 days) administration to the rat did not significantly (p > 0.05) modify the glycemia, prothrombin and partial thromboplastin times, the hypoglycemic effect of phenformin (2.5 mg/kg/die os for 4 days) and glibenclamide (0.5 mg/kg/die os for 4 days) or the anticoagulant effect of warfarin (0.5 mg/kg/die os for 4 days); moreover it did not significantly (p > 0.05) modify the pharmacokinetics of aminophylline (5 mg/kg i.v.) on the rabbit. In conclusion our results documented that teicoplanin does not interfere with phenformin, glibenclamide, or sodium warfarin activities nor with aminophylline pharmacokinetics.
The effect of ticarcillin/clavulanic acid, taken for 7 days as vials containing 1000 mg of ticarcillin and 200 mg of clavulanic acid twice daily intramuscularly, on the steady-state pharmacokinetics of theophylline was studied in 12 patients suffering from acute exacerbation of chronic obstructive pulmonary disease. Initially, patients were treated for four days with theophylline as sustained-release formulation in the amount of 600 mg daily; on the last day, blood samples were taken for theophylline determination. Theophylline concentrations were measured serially for 12 hours by the method of polarized immunofluorescence (Abbott TDx system). Subsequently, while theophylline was continued at the same dosage, each patient received in addition ticarcillin/clavulanic acid vials every 12 hours. After seven days of this combined medication, the serial assays of plasma were repeated at the same time intervals as before. No influence of ticarcillin/clavulanic acid was detectable on the steady-state theophylline pharmacokinetics. It is concluded that both drugs can be administered concomitantly without any dosage adjustment of theophylline.
The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.
1. Neostigmine and BW284C51 induced concentration-dependent contractions in human isolated bronchial preparations whereas tetraisopropylpyrophosphoramide (iso-OMPA) was inactive on airway resting tone. 2. Neostigmine (0.1 microM) or iso-OMPA (100 microM) increased acetylcholine sensitivity in human isolated bronchial preparations but did not alter methacholine or carbachol concentration-effect curves. 3. In the presence of iso-OMPA (10 microM) the bronchial rings were more sensitive to neostigmine. The pD2 values were, control: 6.05 +/- 0.15 and treated: 6.91 +/- 0.14. 4. Neostigmine or iso-OMPA retarded the degradation of acetylcholine when this substrate was exogenously added to human isolated airways. A marked reduction of acetylcholine degradation was observed in the presence of both inhibitors. Exogenous butyrylcholine degradation was prevented by iso-OMPA (10 microM) but not by neostigmine (0.1 microM). 5. These results suggest the presence of butyrylcholinesterase activity in human bronchial muscle and this enzyme may co-regulate the degradation of acetylcholine in this tissue.
Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5 degrees C) for 1-3 weeks. The renin-angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II1 receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25 degrees C while the remaining three groups were exposed to cold (5 degrees C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed.(ABSTRACT TRUNCATED AT 250 WORDS)
Preliminary reports suggest that some pharmacologic agents may be effective in ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and, perhaps, allowing continuing use of ACE inhibitors in patients for whom this class of medication is important. We examined the effect of a once-a-day theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of the cough reflex to capsaicin in 10 hypertensive patients who had developed cough during treatment with an ACE inhibitor. Theophylline did not induce bronchodilation but induced complete remission of clinical symptoms in 8 and attenuated the capsaicin-induced cough number in 7 subjects when compared with placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced cough.
The influence of the epithelium on the contractile responses of bovine bronchial rings to acetylcholine, carbachol, 5-hydroxytryptamine and histamine was studied. Epithelium removal caused a significant leftward shift of the acetylcholine concentration-effect curve, pD2 values were 2.86 +/- 0.11 and 3.34 +/- 0.18 for intact and rubbed tissue, respectively (P < 0.05). However, there was no change in the acetylcholine maximal response. The sensitivity and responsiveness of the bovine bronchus to the other spasmogens were not significantly altered by removal of the epithelium. These results suggest that the epithelium of bovine bronchi modulates only acetylcholine-induced contraction.