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Showing papers by "University of Naples Federico II published in 1991"


Journal ArticleDOI
TL;DR: Serotonin has a vasodilating effect on normal human coronary arteries; when the endothelium is damaged, as in coronary artery disease, serotonin has a direct, unopposed vasoconstricting effect; and platelet-derived factors such as serotonin may have a role in certain acute coronary ischemic syndromes.
Abstract: Background. Studies in animals have shown that serotonin constricts coronary arteries if the endothelium is damaged, but in vitro studies have revealed a vasodilating effect on isolated coronary segments with an intact endothelium. To investigate the effect of serotonin in humans, we studied coronary-artery cross-sectional area and blood flow before and after the infusion of serotonin in seven patients with angiographically normal coronary arteries and in seven with coronary artery disease. Methods. We measured the cross-sectional area of the coronary artery by quantitative angiography and coronary blood flow with an intracoronary Doppler catheter. Measurements were obtained at base line and during intracoronary infusions of serotonin (0.1, 1, and 10 μg per kilogram of body weight per minute, for two minutes). We repeated the measurements after an infusion of ketanserin, an antagonist of serotonin receptors that is thought to block the effect of serotonin on receptors in the arterial wall but not...

426 citations


Journal ArticleDOI
TL;DR: Comparisons between potato RFLP maps derived from different genetic backgrounds revealed conservation of marker order but differences in chromosome and total map length, and significant reduction of map length was observed in interspecific compared to intraspecific crosses.
Abstract: An RFLP linkage map of the potato is presented which comprises 304 loci derived from 230 DNA probes and one morphological marker (tuber skin color) The self-incompatibility locus of potato was mapped to chromosome I, which is homoeologous to tomato chromosome I By mapping chromosome-specific tomato RFLP markers in potato and, vice versa, potato markers in tomato, the different potato and tomato RFLP maps were aligned to each other and the similarity of the potato and tomato genome was confirmed The numbers given to the 12 potato chromosomes are now in accordance with the established tomato nomenclature Comparisons between potato RFLP maps derived from different genetic backgrounds revealed conservation of marker order but differences in chromosome and total map length In particular, significant reduction of map length was observed in interspecific compared to intraspecific crosses The distribution of regions with distorted segregation ratios in the genome was analyzed for four potato parents The most prominent distortion of recombination was found to be caused by the self-incompatibility locus

403 citations


Journal ArticleDOI
03 Jan 1991-Nature
TL;DR: An analysis of several rearranged human X chromosomes is reported and a minimal region of overlap is defined that is consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing the XIC region.
Abstract: X-CHROMOSOME inactivation results in the strictly cis-limited inactivation of many but not all genes on one of the two X chromosomes during early development in somatic cells of mammalian females1. One feature of virtually all models of X inactivation is the existence of an X-inactivation centre (XIC) required in cis for inactivation to occur2–5. This concept predicts that all structurally abnormal X chromosomes capable of being inactivated have in common a defineable region of the X chromosome6–8. Here we report an analysis of several such rearranged human X chromosomes and define a minimal region of overlap. The results are consistent with models invoking a single XIC and provide a molecular foothold for cloning and analysing theXIC region. One of the markers that defines this region is theXIST gene9, which is expressed specifically from inactive, but not active, X chromosomes. The localization of the XIST gene to theXIC region on the human X chromosome implicates XIST in some aspect of X inactivation.

375 citations


Journal ArticleDOI
TL;DR: In this article, a study of both parallel flow and cross-flow in the viscous sublayer generated by a fluid streaming along a grooved surface is presented, with the aim of clarifying the phenomena that underlie the reduction of turbulent drag by such surfaces.
Abstract: A study is undertaken of both parallel flow and cross-flow in the viscous sublayer generated by a fluid streaming along a grooved surface, with the aim of clarifying the phenomena that underlie the reduction of turbulent drag by such surfaces. A quantitative characterization of the effectiveness of different groove profiles in retarding secondary cross-flow is given in terms of the difference of two ‘protrusion heights’. Analytical calculations of limit cases and a boundary-element computer code for the analysis of general profiles are illustrated, and several examples are presented and discussed.

297 citations


Journal ArticleDOI
TL;DR: Data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow.
Abstract: To test whether generation of oxygen radicals during postischemic reperfusion might promote peroxidation of cardiac membrane lipids, four groups of Langendorff-perfused rabbit hearts were processed at the end of (a) control perfusion, (b) 30 min of total global ischemia at 37 degrees C without reperfusion, (c) 30 min of ischemia followed by reperfusion with standard perfusate, (d) 30 min of ischemia followed by reperfusion with the oxygen radical scavenger human recombinant superoxide dismutase (h-SOD). The left ventricle was homogenized and tissue content of malonyldialdehyde (MDA), an end product of lipid peroxidation, was measured on the whole homogenate as well as on various subcellular fractions. Reperfusion was accompanied by a significant increase in MDA content of the whole homogenate and of the fraction enriched in mitochondria and lysosomes. This phenomenon was not observed in hearts subjected to ischemia but not reperfused, and was similarly absent in those hearts which received h-SOD at reflow. Reperfused hearts also had significantly greater levels of conjugated dienes (another marker of lipid peroxidation) in the mitochondrial-lysosomal fraction. Again, this phenomenon did not occur in ischemic hearts or in reperfused hearts treated with h-SOD. Unlike the effect on tissue MDA and conjugated dienes, reperfusion did not significantly stimulate release of MDA in the cardiac effluent. Treatment with h-SOD was also associated with significant improvement in the recovery of cardiac function. In conclusion, these data directly demonstrate that postischemic reperfusion results in enhanced lipid peroxidation of cardiac membranes, which can be blocked by h-SOD, and therefore is most likely secondary to oxygen radical generation at reflow.

265 citations


Journal ArticleDOI
TL;DR: It is demonstrated that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile gly cosylation, the first step of the Maillard reaction.
Abstract: Objective This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. Research Design and Methods Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA 1 , and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients. Results Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA 1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA 1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA 1 levels, stable HbA 1 , and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration. Conclusions These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.

257 citations


Journal ArticleDOI
TL;DR: Gastroenteritis caused by enterotoxigenic E. coli and shigella resistant to a number of drugs was a major problem that frequently interfered with the duties of U.S. troops during Operation Desert Shield.
Abstract: Background. Under combat conditions infectious disease can become a major threat to military forces. During Operation Desert Shield, there were numerous outbreaks of diarrhea among the U.S. forces. To evaluate the causes of and risk factors for diarrheal disease, we collected clinical and epidemiologic data from U.S. troops stationed in northeastern Saudi Arabia. Methods. 432 military personnel who presented with diarrhea, cramps, vomiting, or hematochezia. In addition, a questionnaire was administered to 2022 soldiers in U.S. military units located in various regions of Saudi Arabia. Results. A bacterial enteric pathogen was identified in 49.5 percent of the troops with gastroenteritis. Enterotoxigenic Escherichia coli and Shigella sonnei were the most common bacterial pathogens. Of 125 E. coli infections, 39 percent were resistant to trimethoprim–sulfamethoxazole, 63 percent to tetracycline, and 48 percent to ampicillin. Of 113 shigella infections, 85 percent were resistant to trimethoprim–sulf...

252 citations


Journal ArticleDOI
TL;DR: MR imaging can be sensitive and specific for osteomyelitis if characteristic appearances and pitfall diagnoses are incorporated into the diagnostic criteria.
Abstract: Prospective and retrospective magnetic resonance (MR) imaging (0.35-T) interpretations were compared with final diagnoses in 110 patients suspected to have osteomyelitis. Diagnostic criteria of dark marrow on T1-weighted images and bright marrow on short-tau inversion-recovery images yielded a prospective sensitivity of 98% and a prospective specificity of 75%. Sixty percent of uncomplicated septic joint effusions demonstrated abnormal marrow signal intensity that was mistaken for osteomyelitis. Retrospective review revealed that overall specificity could be improved to 82% without loss of sensitivity if increased marrow signal intensity on T2-weighted images were included as an additional criterion. Specificity may be further increased by use of knowledge of morphologic patterns that distinguish various forms of osteomyelitis. Ten patients (9%) had potential pitfall diagnoses (eg, fracture, infarction, healed infection) that mimic osteomyelitis. MR imaging can be sensitive and specific for osteomyelitis ...

239 citations


Journal ArticleDOI
TL;DR: Results suggest that the depigmenting activity of HQ may partly be related to the ability of the compound to act as an alternate substrate of tyrosinase, thereby competing for tyrosine oxidation in active melanocytes.

203 citations


Journal ArticleDOI
TL;DR: A balanced increase in consumption of fiber-rich foods and unsaturated fat is the most rational way to replace foods rich in saturated fat and cholesterol in the diabetic diet.
Abstract: Dietary recommendations for the treatment of diabetic patients issued by national and international diabetes associations consistently emphasize the need to increase carbohydrate consumption. However, these recommendations have been questioned on the basis of growing evidence that, in both insulin-dependent and non-insulin-dependent diabetic patients, a high-carbohydrate diet does not offer any advantage in terms of blood glucose and plasma lipid concentrations compared with a high-fat (mainly unsaturated) diet. It has been shown repeatedly that a high-carbohydrate diet increases plasma insulin and triglyceride levels and can deteriorate blood glucose control in the postprandial period. However, much of the controversy between advocates and detractors of dietary carbohydrate can be settled by taking into account dietary fiber. Several studies have shown that the adverse metabolic effects of high-carbohydrate diets are neutralized when fiber and carbohydrate are increased simultaneously in the diet for diabetic patients. In particular, these studies demonstrated that a high-carbohydrate/high-fiber diet significantly improves blood glucose control and reduces plasma cholesterol levels in diabetic patients compared with a low-carbohydrate/low-fiber diet. In addition, a high-carbohydrate/high-fiber diet does not increase plasma insulin and triglyceride concentrations, despite the higher consumption of carbohydrates. Unfortunately, dietary fiber represents a heterogenous category, and there is still much to understand as to which foods should be preferred to maximize the metabolic effects of fiber. There are indications that only water-soluble fiber is active on plasma glucose and lipoprotein metabolism in humans. Therefore, in practice, the consumption of legumes, vegetables, and fruits--rich in water-soluble fiber--should be particularly encouraged. The mechanisms by which dietary fiber exerts its hypoglycemic and hypolipidemic activities are unknown. However, the ability of dietary fiber to retard food digestion and nutrient absorption certainly has an important influence on lipid and carbohydrate metabolism. The beneficial effects of high-fiber foods are also exerted by some foods not particularly rich in fiber. The fiber content and physical form of the food can influence the accessibility of nutrients by digestive enzymes, thus delaying digestion and absorption. The identification of these foods with a low-glycemic response would help enlarge the list of foods particularly suitable for diabetic patients. In conclusion, a diet low in cholesterol and saturated fat should be recommended to all diabetic patients to prevent cardiovascular disease. A balanced increase in consumption of fiber-rich foods and unsaturated fat is the most rational way to replace foods rich in saturated fat and cholesterol in the diabetic diet.

191 citations


Journal ArticleDOI
TL;DR: Two different chromosomal locations of major genes controlling extreme resistance to potato virus X (PVX) were found by restriction fragment length polymorphism (RFLP) analysis of two populations segregating for the resistance.
Abstract: Two different chromosomal locations of major genes controlling extreme resistance to potato virus X (PVX) were found by restriction fragment length polymorphism (RFLP) analysis of two populations segregating for the resistance. The resistance geneRx1 mapped to the distal end of chromosome XII, whereasRx2 was located at an intermediate position on linkage group V in a region where reduced recombination and segregation distortion have also been observed. These linkage anomalies were due to abnormal behaviour of the chromosome contributed by the resistant parent P34. The results presented were obtained using two different strategies for mapping genes of unknown location. One approach was the use of probes revealing polymorphic loci spread throughout the genome and resulted in the mapping ofRx1. The second approach was based on the assumption of possible linkage between the resistance gene and clone-specific DNA fragments introduced from a wild potato species.Rx2 was mapped by adopting this strategy.

Journal ArticleDOI
01 Apr 1991
TL;DR: Modelling the clutter as a compound Gaussian or a spherically invariant random process allows a complete specification of the clutter suitable for use in radar design and lends itself readily to computer simulation procedures.
Abstract: As the undesired echo from a radar environment (clutter) is often not Rayleigh distributed, problems arise in specifying the clutter as a non-Gaussian random process and in computer-generating realisations of clutter for simulation purposes. The paper shows that modelling the clutter as a compound Gaussian or a spherically invariant random process allows a complete specification of the clutter suitable for use in radar design. It also lends itself readily to computer simulation procedures. Specific procedures for generating clutter realisations with assigned correlation properties and with K or Weibull amplitude distributions are suggested, and are validated by statistical tests. Then the issue of resolving between the Weibull and K distributions is considered, and empirical operative characteristics of the associated hypothesis test are computed.

Journal ArticleDOI
TL;DR: Euglycemic hyperinsulinemic glucose clamp produced a lower insulin-mediated inhibition of endogenous (hepatic) glucose production (HGP) and a greater increase in both glucose disappearance rate (Rd) and glucose metabolic clearance rate (gMCR) in patients than in controls during the first two insulin infusion rates.
Abstract: Congestive heart failure is a condition associated with increased plasma norepinephrine levels. Moreover, norepinephrine has been recently demonstrated to affect glucose homeostasis by decreasing insulin sensitivity. In the present study, eight patients suffering from chronic congestive heart failure and 10 healthy age- and body mass index-matched subjected were submitted to both an oral glucose tolerance test (OGTT; 75 g) and a euglycemic hyperinsulinemic glucose clamp. During the 360 minutes of the glucose clamp, insulin was infused at three different rates (25, 50, and 100 mU/kg/h), while d - 3 H glucose infusion allowed determination of glucose turnover. In basal conditions, patients versus controls had similar plasma glucose (5.2 ± 0.1 v 4.9 ± 0.2 mmol/L, P = NS), but higher plasma insulin (125.7 ± 9.2 v 35.7 ± 3.3 pmol/L, P v 1.47 ± 0.22 nmol/L, P v 792 ± 88 μ mol/L, P r = .65, P

Journal ArticleDOI
01 Aug 1991-Gut
TL;DR: A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state.
Abstract: A cohort of 123 patients with coeliac disease, diagnosed in the first three years of life and followed up for at least 10 years, was reevaluated during the teenage period in terms of compliance with the diet and clinical state. Mucosal structure and lymphocytes were assessed in small intestinal biopsy specimens obtained from 36 subjects, by computerised image analysis. Of these adolescents with coeliac disease, 65% were adhering to a strict gluten free diet, 11.4% were on a gluten free diet but with occasional gluten intake, and 23.6% were on a gluten containing diet. Clinical symptoms occurred more frequently in patients on a gluten containing diet, but not in patients on a semi-strict diet. Occasional intake of small amounts (0.06-2 g/day) of gluten did not produce increased concentrations of antigliadin antibodies but resulted in an appreciably increased crypt epithelial volume and expanded crypt intraepithelial lymphocyte population.

Journal ArticleDOI
TL;DR: The expression system described in the present work has the main advantage of producing a high yield of recombinant human interleukin-6 (about 25 mg/l) combined with a very simple purification scheme.
Abstract: Human interleukin-6 or B-cell stimulatory factor-2 is a cytokine involved in acute phase and immune response. Cloning of cDNA for human interleukin-6 in the pT7.7 expression plasmid under the control of a bacteriophage T7 RNA polymerase promoter system allows rapid production of the cytokine in Escherichia coli. Upon cell induction with isopropyl thiogalactopyranoside, recombinant human interleukin-6 is overexpressed and forms insoluble inclusion bodies. Solubilization of the protein with 6 M guanidine hydrochloride and refolding in the presence of a reduction/oxidation system results in a quantitative recovery of recombinant human interleukin-6. This material is already 70% pure and can be further purified to homogeneity with a single passage over a weak anionic-exchange column. Extended structural characterization of the purified protein by electrospray mass spectrometry, automated Edman degradation and peptide mapping by high-pressure liquid chromatography/fast-atom-bombardment mass spectrometry demonstrates that recombinant human interleukin-6 is identical to the natural protein both in amino acid sequence and S-S bridge content. However, it contains a minor component accounting for about 20% of the entire translated protein which exhibits a Met-Ala dipeptide extension at the N-terminus. Purified recombinant human interleukin-6 is biologically active because it is able to induce at least 70-fold the human C-reactive promoter transfected in human hepatoma Hep 3B cells and is stable for several months in 10% glycerol at 4 degrees C. The expression system described in the present work has the main advantage of producing a high yield of recombinant human interleukin-6 (about 25 mg/l) combined with a very simple purification scheme.

Journal ArticleDOI
TL;DR: Bioassay-directed fractionation of the anti-inflammatory extracts of Uncaria tomentosa, using the carrageenan-induced edema in rat paw, has led to the isolation of a new quinovic acid glycoside 7 as one of the active principles.
Abstract: Bioassay-directed fractionation of the anti-inflammatory extracts of Uncaria tomentosa, using the carrageenan-induced edema in rat paw, has led to the isolation of a new quinovic acid glycoside 7 as one of the active principles. Furthermore, a new triterpene 8 was isolated as its methyl ester. The structures were elucidated by spectral and chemical studies.

Journal ArticleDOI
TL;DR: In this paper, the role of recurrent platelet aggregation in the development of neointimal proliferation of coronary arteries was explored in 24 chronically instrumented dogs, and variable degrees of coronary artery proliferation were observed 3 weeks after mechanical injury of the arterial endothelium and the placement of an external coronary artery constrictor.
Abstract: The role of recurrent platelet aggregation in the development of neointimal proliferation of coronary arteries was explored in this study, and the hypothesis was evaluated that recurrent platelet aggregation and the consequent frequency and severity of cyclic coronary blood flow variations are important pathophysiologic factors in the subsequent development of neointimal proliferation. In 24 chronically instrumented dogs, variable degrees of coronary artery neointimal proliferation were observed 3 weeks after mechanical injury of the arterial endothelium and the placement of an external coronary artery constrictor. The severity of neointimal proliferation at 21 days was closely related to the frequency and severity of cyclic coronary blood flow variations during the initial 7 days after instrumentation of the animals, itself a manifestation of recurrent platelet aggregation and dislodgement. Pharmacological therapy with a dual thromboxane A2 synthetase inhibitor and receptor antagonist and with a serotonin S2 receptor antagonist frequently was successful in abolishing cyclic blood flow variations and in retarding neointimal proliferation.

Journal ArticleDOI
TL;DR: This review focuses on two serious bullous drug reactions that more and more frequently have appeared in recent dermatologic reports: pemphigus and bullous pemPHigoid.
Abstract: The consumption of drugs is increasing worldwide. The greater it becomes, the more we have to reckon with cutaneous side effects. Lately, bullous drug eruptions have seemed to predominate over others; this may be connected with the widespread use of potent new drugs that, in certain conditions, prove to be capable of causing intraepidermal or dermo-epidermal detachment. This review focuses on two serious bullous drug reactions that more and more frequently have appeared in recent dermatologic reports: pemphigus and bullous pemphigoid.


Journal ArticleDOI
TL;DR: The RNase found in bull semen, although a member of the mammalian superfamily of ribonucleases, possesses some unusual properties and displays antispermatogenic, antitumor and immunosuppressive activities.

Journal ArticleDOI
TL;DR: MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional glial, and rhabdomyoblastic differentiation, and no photoreceptor differentiation and probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.
Abstract: Ten cases of melanotic neuroectodermal tumor of infancy (MNTI) were studied. There were nine males and one female ranging in age from 2 weeks to 10 months; one patient was 8 years old. Sites of origin were the maxilla (five), epididymis (two), mandible (one), skull (one), and soft tissues of the cheek (one). Six tumors recurred from 1 to 18 months after diagnosis. One patient had widespread dissemination. Electron microscopic study of four cases showed cells with melanosomes at various stages of maturation, and cells with neuroblastic features, including neurosecretory granules and cytoplasmic processes. Nine cases of MNTI were studied immunohistochemically. Small neuroblastic cells and large cells in all cases were reactive for neuron-specific enolase (NSE), synaptophysin, HMB45, and dopamine-beta-hydroxylase, large cells in all cases and few small cells were reactive for cytokeratin (CK) and vimentin (VIM). Epithelial membrane antigen was observed in large cells in three cases, four cases expressed Leu 7 antigen, three were focally positive for glial fibrillary acidic protein, one for desmin, and one for chromogranin. All cases were nonreactive for retinol-binding protein, neurofilaments, alpha-fetoprotein, S-100 protein, and carcinoembryonic antigen. Five normal adult retinas were studied similarly; the pigmented epithelium of the retina was reactive for CK, VIM, HMB45, NSE, and S-100. DNA study, performed in eight tumors, revealed aneuploidy in two (DNA index = 1.7 and 1.8); these cases recurred within 1 month. No differences were observed according to site or behavior. MNTI is a primitive neuroectodermal tumor with polyphenotypic expression of neural and epithelial markers, melanin production, occasional glial, and rhabdomyoblastic differentiation, and no photoreceptor differentiation. It probably represents a dysembryogenetic neoplasm that recapitulates the retina at 5 weeks of gestation.

Journal ArticleDOI
TL;DR: It is shown that ERV-9 LTR sequences are capable to drive expression of linked CAT gene in a cell specific manner as LTR promoter activity has been detected only in NT2/D1 cells.
Abstract: A novel endogenous retroviral sequence (ERV-9) has been isolated from a human embryonal carcinoma cDNA library by hybridization to a probe containing a recently described human repetitive element. DNA sequence analysis of the 4kb cDNA insert (pHE.1) revealed the presence of ORFs potentially coding for putative retrovirus-related gag, pol and env proteins. Northern blot and RNase protection experiments showed that RNA homologous to the pHE.1 insert is detected only in embryonal carcinoma cells as a 8 kb mRNA, and its expression is negatively regulated during retinoic acid induced differentiation of the human teratocarcinoma cell line NT2/D1. Using a pol specific probe we have isolated a genomic locus containing the ERV-9 sequences. Characterization by restriction enzyme analysis and DNA sequencing allowed us to define LTR-like sequences, that are composed by a complex array of subrepetitive elements. In addition we show that ERV-9 LTR sequences are capable to drive expression of linked CAT gene in a cell specific manner as LTR promoter activity has been detected only in NT2/D1 cells.

Journal Article
TL;DR: The data indicate that FK-506 is a potent antiinflammatory agent that acts on human basophils presumably by binding to a receptor site (i.e., Fk-506 binding protein).
Abstract: FK-506, a macrolide that binds with high affinity to a specific binding protein, and the structurally related macrolide rapamycin (RAP) were compared to cyclosporin A (CsA) for their effects on the release of preformed (histamine) and de novo synthesized (peptide leukotriene C4) inflammatory mediators from human basophils. FK-506 (1 to 300 nM) concentration dependently inhibited histamine release from basophils activated by Der p I Ag, anti-IgE, or compound A23187. FK-506 was more potent than CsA when basophils were challenged with Ag (IC50 = 25.5 +/- 9.5 vs 834.3 +/- 79.8 nM; p less than 0.001), anti-IgE (IC50 = 9.4 +/- 1.7 vs 441.3 +/- 106.7 nM; p less than 0.001), and A23187 (IC50 = 4.1 +/- 0.9 vs 36.7 +/- 3.8 nM; p less than 0.001). The maximal inhibitory effect of FK-506 was higher than that caused by CsA when basophils were activated by Der p I (80.0 +/- 3.6 vs 49.5 +/- 4.7%; p less than 0.001) and anti-IgE (90.4 +/- 1.8 vs 62.3 +/- 2.9%; p less than 0.001). FK-506 had little or no effect on the release of histamine caused by f-met peptide, phorbol myristate (12-tetradecanoyloxy-13-acetoxy-phorbol), and bryostatin 1. RAP (30 to 1000 nM) selectively inhibited only IgE-mediated histamine release from basophils, although it had no effect on mediator release caused by f-met peptide, A23187, 12-tetradecanoyloxy-13-acetoxy-phorbol, and bryostatin 1. FK-506 also inhibited the de novo synthesis of sulfidopeptide leukotriene C4 from basophils challenged with anti-IgE. Low concentrations of FK-506 and CsA synergistically inhibited the release of mediators from basophils induced by anti-IgE or compound A23187. IL-3 (3 and 10 ng/ml), but not IL-1 beta (10 and 100 ng/ml), reversed the inhibitory effect of both FK-506 and CsA on basophils challenged with anti-IgE or A23187. RAP was a competitive antagonist of the inhibitory effect of FK-506 on A23187-induced histamine release from basophils with a dissociation constant of about 30 nM. In contrast, RAP did not modify the inhibitory effect of CsA on A23187-induced histamine release. These data indicate that FK-506 is a potent antiinflammatory agent that acts on human basophils presumably by binding to a receptor site (i.e., FK-506 binding protein).

Journal ArticleDOI
TL;DR: Increasing the dietary potassium intake from natural foods is a feasible and effective measure to reduce antihypertensive drug treatment.
Abstract: ▪Objective:To determine whether an increase in dietary potassium intake from natural foods reduces the need for antihypertensive medication in patients with essential hypertension. ▪Design...

Journal ArticleDOI
TL;DR: The possibility that peroxidase, rather than, or in addition to, tyrosinase, may play a critical role in the later stages of the biosynthesis of melanins is raised.

Journal ArticleDOI
TL;DR: Fourteen articles by different authors describe digital audio and computer music systems made possible by advances in digital signal processing theory, hardware design, and programming techniques.
Abstract: Fourteen articles by different authors describe digital audio and computer music systems made possible by advances in digital signal processing theory, hardware design, and programming techniques. They focus on models that combine time-domain and frequency-domain representations (grains, wavelets,

Journal ArticleDOI
TL;DR: The pBrBz- (Aib)10-OtBu, synthesized by the 5(4H)-oxazolone method, crystallizes in the monoclinic space group C2/c with a = 43.901(2), b = 9.289(2) and c = 34.746(3) A; β = 114.69 (3)°; and Z = 8.073 for 6819 observed reflections as mentioned in this paper.
Abstract: The decapeptide pBrBz- (Aib)10-OtBu, synthesized by the 5(4H)-oxazolone method, crystallizes in the monoclinic space group C2/c with a = 43.901(2), b = 9.289(2), and c = 34.746(3) A; β = 114.69(3)°; and Z = 8. The crystals contain one molecule of water associated with each peptide. The structure has been solved by the Patterson method and refined to an R value of 0.073 for 6819 observed reflections. The peptide adopts a regular 310-helical structure stabilized by eight NH … OC intramolecular 1 4 (or C10) H bonds. This study has allowed us to characterize this important peptide secondary structure in great detail. The crystal-state conformation agrees well with proposals made on the basis of an ir absorption and 1H-nmr study in solution.

Journal ArticleDOI
TL;DR: It is shown that PPT is enhanced in both lean and obese subjects when LCTs in a mixed meal are replaced with MCTs, and the postprandial response of glucose, insulin, and free fatty acids did not depend on the type of oil contained in the meal.

Journal ArticleDOI
TL;DR: It is concluded that, in man, an adequate pulse frequency is required to allow the appearance of the greater inhibition of pulsatile insulin on endogenous glucose production.
Abstract: The aim of this study was to see if the greater effect of insulin on hepatic glucose output when insulin is given using 13-min pulses in man remains when the same amount of insulin is delivered using 26-min pulses. The study was performed on nine male healthy volunteers submitted to a 325 min glucose-controlled glucose iv infusion using the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin. Three experiments were performed in each subject on different days and in random order. In all cases glucagon was replaced (58 ng min-1). The amounts of insulin infused were identical in all instances and were 0.2 mU kg-1 min-1 (continuous), 1.3 mU kg-1 min-1, 2 min on and 11 min off (13-min pulses) or 2.6 mU kg-1 min-1, 2 min on and 24 min off (26-min pulses). Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator, and classic methodology using D-[3-3H] glucose infusion allowed to study glucose turnover. When compared with continuous insulin, 13-min insulin pulses induced a significantly greater inhibition of endogenous glucose production. This effect disappeared when insulin was delivered in 26-min pulses. We conclude that, in man, an adequate pulse frequency is required to allow the appearance of the greater inhibition of pulsatile insulin on endogenous glucose production.

Journal ArticleDOI
TL;DR: It is shown that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change.