Infections in children following renal transplantation.
Explore the source record for details and available documents.
Age Factors↗
Biomedical subjects
A Alonso
Publications and source records attributed to A Alonso.
Combined heart and kidney transplantation.
Explore the source record for details and available documents.
Adult↗
Structure and functional properties of diacylglycerols in membranes.
1. 1,2-Diacyl-sn-glycerols (DAG) are minor components of cell membranes (about 1 mole% of the lipids) and yet they are potent regulators of both the physical properties of the lipid bilayer and the catalytic behaviour of several membrane-related enzymes. 2. In the pure state DAG's present a considerable polymorphism, with several crystalline phases in addition to the neat fluid phase. The most stable crystalline phase is the so-called beta' phase, a monoclinic crystalline form with orthorhombic perpendicular subcell chain packing, in which both acyl chains lie parallel to each other in a hairpinlike configuration about the sn-1 and sn-2 glycerol carbon atoms. The molecules are organized in a bilayer, with the glycerol backbone roughly parallel to the plane of the bilayer, and the acyl chains tilted at approximately 60 degrees with respect to that plane. Acyl chain unsaturation, and particularly a single cis unsaturation, impairs chain packing in mixed-chain DAG's, and this results in an increased number of metastable crystalline phases. 3. DAG's mix with phospholipids in fluid bilayers when their melting temperature is below or close enough to the melting temperature of the bilayer system. When incorporated in phospholipid bilayers, the conformation of DAG is such that the glycerol backbone is nearly perpendicular to the bilayer, with the sn-1 chain extending from the glycerol Cl carbon into the hydrophobic matrix of the bilayer and the sn-2 chain first extending parallel to the bilayer surface, then making a 90 degrees bend at the position of the sn-1 carbonyl to become parallel to the sn-1 chain. DAG's are located in phospholipid bilayers about two CH2 units deeper than the adjacent phospholipids. DAG's mix nonideally with phospholipids, giving rise to in-plane separations of DAG-rich and -poor domains, even in the fluid state. DAG molecules also increase the separation between phospholipid headgroups, and decrease the hydration of the bilayer surface. Also, because the transversal section of the DAG headgroup is small when compared to that of the acyl chains, DAG favours the (negative) curvature of the lipid monolayers, and DAG-phospholipid mixtures tend to convert into inverted nonlamellar hexagonal or cubic phases. 4. A number of membrane enzyme activities are modulated (activated) by DAG, most notably protein kinase C, phospholipases and other enzymes of lipid metabolism. Protein kinase C activation (and perhaps that of other enzymes as well) occurs as the combined result of a number of DAG-induced modifications of lipid bilayers that include: changes in lipid headgroup conformation, interspacing and hydration, changes in the bilayer propensity to form inverted nonlamellar phases, and lateral phase separations of DAG-rich and -poor domains. Among the DAG-activated enzymes, phospholipases C show the peculiarity of yielding the activator DAG as their reaction product, and this allows the self-induced transition from a low- to a high-activity status. 5. DAG's induce or enhance membrane fusion in a number of ways, mainly through partial dehydration of the bilayer surface, increase in lipid monolayer curvature and perhaps lateral phase separation. DAG-increased fusion rates have been demonstrated in several instances of cation-induced fusion of model membranes, as well as in Ca(2+)-induced fusion of chromaffin granules with plasma membrane vesicles. Also phospholipase C has been shown to induce vesicle aggregation and fusion through the catalytic generation of DAG in the bilayers. A rather general property of DAG is that it promotes vesicular or interparticle aggregation. 6. In the living cell, DAG is often generated through phospholipid degradation in response to an extracellular agonist binding a specific receptor in the cell surface. DAG is said to act as an intracellular second messenger. (ABSTRACT TRUNCATED)
Cell Membrane↗
[The clinical management guidelines of the Sociedad Española de Cardiología in acute myocardial infarct].
In the recent years, new possibilities have emerged in the diagnosis and management of acute myocardial infarction with ST segment elevation and its complications. Moreover, a deep transformation has taken place in the health care system organization, particularly in aspects related to care of patients presenting non-traumatic chest pain, both in pre-hospital and hospital areas. All these issues warrant a consensus document in Spain dealing with the role that these important changes should play in the whole management of myocardial infarction patients. This document revises and updates all the main clinical issues of acute myocardial infarction patients from the moment they contact with the health care system outside the hospital until they return home, after staying at the coronary care unit and the general hospitalization ward. All those aspects are considered not only in the uncomplicated myocardial infarction but also in the complicated one. This review also includes a set of recommendations on structural and organisational aspects, mainly referred to the prehospital and emergency levels.
Cardiology↗
Occupational asthma caused by champignon flies.
BACKGROUND: Occupational bronchial asthma in mushroom (champignon) workers is unusual, although reports on it appeared in 1938 and 1951; we have not found any others since those dates. Here we report the case of a 52-year-old man who works as a champignon cultivator. He suffered rhinoconjunctivitis and asthma attacks whenever he entered the champignon culture caves. We studied flies as a possible antigen source. We collected these insects from the growing sites in order to identify them, and then prepare an extract; the samples turned out to be of two families of insects of the order Diptera, 98% from the Phoridae family (Brachycera suborder) and 2% from the Sciaridae (Nematocera suborder). METHODS: Skin prick tests, conjunctival provocation tests, serum specific IgE, specific IgE-binding fractions in immunoblotting, and monitoring of PEFR (at work and off work) were performed. RESULTS: IgE-mediated hypersensitivity to these flies was demonstrated by skin prick test, conjunctival provocation test, serum specific IgE, and IgE-binding fractions in immunoblotting. Monitoring of PEFR both at work and off work showed a clear relationship between symptoms, or fall in PEFR, and the workplace. CONCLUSIONS: We report the case of a patient suffering from asthma and rhinoconjunctivitis caused by hypersensitivity to fly proteins.
Agaricales↗
Dietary assessment in five cases of allergic reactions due to gastroallergic anisakiasis.
BACKGROUND: Anisakis simplex can cause allergic reactions in sensitized patients. Some of these reactions are related to acute parasitism, as is shown in gastroallergic anisakiasis (anisakiasis with digestive and predominantly allergic symptoms). At present, a nonseafood diet is recommended for all patients with any kind of A. simplex allergy. We wished to confirm the clinical suspicion that patients with allergic symptoms after ingestion of raw or undercooked seafood who are sensitized to A. simplex, and diagnosed with gastroallergic anisakiasis, can tolerate the ingestion of seafood when the parasites are dead and noninfective. METHODS: We included patients diagnosed with gastroallergic anisakiasis (positive skin prick test or/and serum specific IgE to A. simplex, with one or more parasites found by gastroscopy in the stomach). Patients included in the study gave written, informed consent. Specimens of A. simplex about 2 cm long were selected, placed in capsules, and frozen at -20 degrees C for more than 48 h to make them noninfective. We administered 11 specimens to every patient at the hospital. If they tolerated the larvae, they were told to eat well-frozen seafood (-20 degrees C at least 48 h). After 6 months, the patients were re-evaluated. RESULTS: Five patients accepted the challenge with noninfective A. simplex larvae. All tolerated the noninfective larvae. After eating deep-frozen seafood for 6 months, no patient suffered a reaction. CONCLUSIONS: In gastroallergic anisakiasis, the antigens of the live parasite probably cause the allergic symptoms. Patients with this disease can tolerate deep-frozen seafood, in which the parasites are dead.
Adult↗
DQB1*0602 confers genetic susceptibility to multiple sclerosis in Afro-Brazilians.
We studied the distribution of the HLA-DRB1, -DQA1 and -DQB1 alleles in 44 Afro-Brazilian patients with multiple sclerosis and 88 controls. Although no significant differences were found between the patients and controls for the DRB1 and DQA1 alleles, the HLA-DQB1*0602 allele was positively associated with multiple sclerosis (45.0% vs. 17.0%, Pc=0.024, RR=3.31). The positive extended haplotypes for DQB1*0602 were more frequent in patients than controls, although the differences were not statistically significant in any of them. These results in Afro-Brazilians are in line with other studies which have found DQB1*0602 to be associated with the disease in the absence of the DRB1*1501 allele. We therefore think that the association with the disease in this ethnic group is more allelic than haplotypic.
Alleles↗
4-trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid, are potent inhibitors of nuclear factor kappaB activation.
1. The effect of two derivatives of salicylate, 2-hydroxy-4-trifluoromethylbenzoic acid (HTB) and 2-acetoxy-4-trifluoromethylbenzoic acid (triflusal), on the activation of NF-kappaB elicited by tumour necrosis factor-alpha (TNF-alpha) on human umbilical vein endothelial cells (HUVEC) was tested. 2. The expression of the mRNA of vascular cell adhesion molecule-1 (VCAM-1) was studied as an example of a gene the expression of which is regulated by NF-kappaB. To extend these findings to other systems, the induction of nitric oxide synthase in rat adherent peritoneal macrophages was studied. 3. Both HTB and triflusal were more potent than aspirin or salicylate as inhibitors of the nuclear translocation of NF-kappaB. The calculation of the IC50 values showed approximately 2 mM for HTB, 4 mM for aspirin and >4 mM for salicylate. 4. Comparison of the potency of these compounds on VCAM-1 mRNA expression showed complete inhibition by both triflusal and HTB at a concentration of 4 mM whereas aspirin and salicylate produced only 36-43% inhibition at the same concentration. 5. Inhibition of NF-kappaB activation was also observed in rat peritoneal macrophages stimulated via their receptors for the Fc portion of the antibody molecule with IgG/ovalbumin immune complexes. This was accompanied by a dose-dependent inhibition of nitrite production by the L-arginine pathway via iNOS. IC50 values for this effect were 1.13+/-0.12 mM (triflusal), 1.84+/-0.34 (HTB), 6.08+/-1.53 mM (aspirin) and 9.16+/-1.9 mM (salicylate). 6. These data indicate that the incorporation of a 4-trifluoromethyl group to the salicylate molecule strongly enhances its inhibitory effect on NF-kappaB activation, VCAM-1 mRNA expression and iNOS induction, irrespective of the presence of the acetyl moiety involved in the inhibition of cyclo-oxygenase.
Animals↗
Environmental and clinical isolates of Pseudomonas aeruginosa show pathogenic and biodegradative properties irrespective of their origin.
Virulence properties of pathogenic bacteria, as well as resistance to antibiotics, are thought to arise through a specialization process favoured by the strong selection pressure imposed in clinical treatments. Nevertheless, in the case of opportunistic pathogens, it is unclear whether strains can be classified into virulent and non-virulent isolates. Clones of the opportunistic pathogen Pseudomonas aeruginosa do not seem to be associated to a particular biovar or pathovar, which suggests that virulence characteristics in opportunistic pathogens may already be present in environmental (non-clinical) isolates. We have explored this possibility, studying environmental isolates (mainly from oil-contaminated soils) and clinical isolates (from bacteraemia and cystic fibrosis patients) of P. aeruginosa. All environmental strains were found to actively efflux quinolones, which are synthetic antibiotics not expected to be present in the environment. These strains contained multidrug resistance determinants, were capable of invading epithelial cells and presented genes from the quorum-sensing and type III secretion systems. Some of them expressed either haemolytic or proteolytic activities or both, characteristics considered to be typical of virulent strains. All the strains tested, of clinical or environmental origin, could use alkanes (oil hydrocarbons) as a carbon source. Our results suggest that clinical and non-clinical P. aeruginosa strains might be functionally equivalent in several traits relevant for their virulence or environmental properties. Selection of clinically relevant traits, such as antibiotic resistance or cellular invasiveness, in opportunistic pathogens present in soil ecosystems is discussed.
Animals↗
The human papillomavirus type 11 upstream regulatory region triggers hair-follicle-specific gene expression in transgenic mice.
We have generated transgenic mice carrying the URR of the human papillomavirus type 11 ligated in front of the Escherichia coli beta-galactosidase coding region sequence. Using X-Gal staining to demonstrate beta-galactosidase production, we observed a hair-specific transcription of the reporter gene. This transcription was limited to the epithelial cells of the hair bulge region. The transgene was developmentally regulated, as no LacZ staining was demonstrated during embryogenesis and specific staining was first observed after birth. Surprisingly, dexamethasone and ultraviolet B, but not phorbol myristate acetate or progesterone treatment of the animals resulted in an increase in number and intensity of hair follicles expressing the reporter gene.
Animals↗
Biophysical properties and slow voltage-dependent inactivation of a sustained sodium current in entorhinal cortex layer-II principal neurons: a whole-cell and single-channel study.
The functional and biophysical properties of a sustained, or "persistent," Na(+) current (I(NaP)) responsible for the generation of subthreshold oscillatory activity in entorhinal cortex layer-II principal neurons (the "stellate cells") were investigated with whole-cell, patch-clamp experiments. Both acutely dissociated cells and slices derived from adult rat entorhinal cortex were used. I(NaP), activated by either slow voltage ramps or long-lasting depolarizing pulses, was prominent in both isolated and, especially, in situ neurons. The analysis of the gating properties of the transient Na(+) current (I(NaT)) in the same neurons revealed that the resulting time-independent "window" current (I(NaTW)) had both amplitude and voltage dependence not compatible with those of the observed I(NaP), thus implying the existence of an alternative mechanism of persistent Na(+)-current generation. The tetrodotoxin-sensitive Na(+) currents evoked by slow voltage ramps decreased in amplitude with decreasing ramp slopes, thus suggesting that a time-dependent inactivation was taking place during ramp depolarizations. When ramps were preceded by increasingly positive, long-lasting voltage prepulses, I(NaP) was progressively, and eventually completely, inactivated. The V(1/2) of I(NaP) steady state inactivation was approximately -49 mV. The time dependence of the development of the inactivation was also studied by varying the duration of the inactivating prepulse: time constants ranging from approximately 6.8 to approximately 2.6 s, depending on the voltage level, were revealed. Moreover, the activation and inactivation properties of I(NaP) were such as to generate, within a relatively broad membrane-voltage range, a really persistent window current (I(NaPW)). Significantly, I(NaPW) was maximal at about the same voltage level at which subthreshold oscillations are expressed by the stellate cells. Indeed, at -50 mV, the I(NaPW) was shown to contribute to >80% of the persistent Na(+) current that sustains the subthreshold oscillations, whereas only the remaining part can be attributed to a classical Hodgkin-Huxley I(NaTW). Finally, the single-channel bases of I(NaP) slow inactivation and I(NaPW) generation were investigated in cell-attached experiments. Both phenomena were found to be underlain by repetitive, relatively prolonged late channel openings that appeared to undergo inactivation in a nearly irreversible manner at high depolarization levels (-10 mV), but not at more negative potentials (-40 mV).
Algorithms↗
Effect of chemokine receptor mutations on heterosexual human immunodeficiency virus transmission.
To assess the effect of mutations at the CCR-2 and CCR-5 loci on heterosexual human immunodeficiency virus (HIV) transmission, 144 persons heterosexually exposed to HIV (infected and uninfected [EU]) and 57 HIV-positive index partners were genotyped. A significantly higher frequency of 64I heterozygotes at CCR-2 was observed in HIV-positive than in EU women (P=.02, relative risk=1.6). The allele frequency of 64I in women was 8% in HIV-positive contacts and 1% in EUs (P<.02). At CCR-5, no difference in the frequency of Delta32 was seen between groups, and the CCR-5 genotypes did not differ in accumulated "at-risk" exposure in EUs. Combining the analysis of the Delta32 and 64I mutations in index partners suggested an additive effect on transmission (P=.10). Thus heterozygosity for 64I at CCR-2 acts as a risk factor for HIV infection of women after heterosexual contact but heterozygosity for Delta32 at CCR-5 has no detectable effect.
Cohort Studies↗
Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa.
Pseudomonas aeruginosa is one of the most important opportunistic pathogens involved in nosocomial infections, cystic fibrosis patients included. Hospital isolates frequently present multidrug-resistance (MDR) phenotypes as the consequence of constant antibiotic selective pressure. The kinetics of emergence of P. aeruginosa MDR mutants under antibiotic selective pressure indicated that long-term incubation in the presence of the bacteriostatic antibiotic tetracycline increases the mutation rate per cell per day of P. aeruginosa PAO1 by several orders of magnitude. The tetracycline-resistant mutants obtained were stable, showed decreased susceptibility to antibiotics belonging to different structural families, and contained an outer-membrane protein not present in the wild-type P. aeruginosa strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa. The results are relevant for understanding the rapid emergence of antibiotic-resistant mutants among bacterial populations during infections. Their relationship to other models of increased mutagenesis under stress is discussed with respect to the adaptive mutation phenomenon.
Anti-Bacterial Agents↗
Outcome analysis of coronary artery bypass grafting: minimally invasive versus standard techniques.
Minimally invasive coronary artery bypass grafting (MIDCAB) procedures are purported to result in improvements in patient management over standard techniques. A comparative study was performed on risk-stratified patients treated with either technique. Following institutional review board approval, a retrospective random chart review was conducted on 27 MIDCAB and 37 standard coronary artery bypass grafting (CABG) patients who were operated on over a 12-month period at the University of Nebraska Medical Center. Risk stratification was accomplished by dividing the two patient populations, MIDCAB and 'standard', into one of four subgroups based on a preoperative risk score. Risk stratification was achieved by dividing the patient populations into one of four subgroups: good, fair, poor and high risk. Both groups received similar operations and surgical interventions, except for the inclusion of cardiopulmonary bypass (CPB). Approximately 200 parameters were collected and analyzed in the following categories: anthropometric, operative and postoperative outcomes. The MIDCAB group had a significantly lower number of vessels bypassed (2.0+/-0.7 vs 3.4+/-0.9, p < 0.0001). Total postoperative blood product transfusions trended higher in the standard group (6.1+/-12.6 U) when compared to the MIDCAB patients (2.3+/-5.5 U, p < 0.15), although not statistically significant. Postoperative inotrope use was significantly less in the MIDCAB group (19% vs 59%, p < 0.002). Ventilator time in the MIDCAB group was 10.5+/-5.4 h vs 15.0+/-12.3 h in the standard group (p < 0.07). The MIDCAB group had an overall greater length of stay, but was only statistically different within the poor-risk subgroup (12.2+/-10.7 vs 7.5+/-3.9, p < 0.04). The results of this study show that when CPB is not utilized in treating patients undergoing CABG procedures, the benefits in regards to patient outcomes are unclear. This necessitates the need for further work when comparing outcomes for risk-stratified patients.
Aged↗
Congenital hydranencephalic-hydrocephalic syndrome associated with mitochondrial dysfunction.
We report the case of a 3-year-old girl, the only child of a nonconsanguineous couple without relevant antecedents, who was born with hydranencephalic-hydrocephalic syndrome diagnosed by ultrasonography at gestation week 28, and who was treated during the neonatal period by implantation of a ventriculoperitoneal shunt. She showed severe mental retardation, and died at age 4 years following an acute respiratory infection. Due to persistently high lactic acid levels in blood, muscle and skin biopsies were taken. Analysis of muscle biopsies revealed microscopic and ultrastructural alterations typical of mitochondrial disorders, and low levels of complexes III and IV of the mitochondrial respiratory chain. The enzymes of the pyruvate dehydrogenase complex showed normal activities in cultured skin fibroblasts. These findings raise the possibility that at least some cases of congenital hydranencephalic-hydrocephalic syndrome may be due to alterations in the mitochondrial respiratory chain.
Biopsy↗
Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite, 2-hydroxy-4-trifluoromethylbenzoic acid.
The therapeutic potential of drugs that block the induction of cyclooxygenase-2 has been emphasized. When two 4-trifluoromethyl salicylate derivatives [2-acetoxy-4-trifluoromethyl-benzoic acid (triflusal) and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid (HTB)] were compared with aspirin and sodium salicylate as cyclooxygenase-2 (COX-2) inhibitors, we observed that in bacterial lipopolysaccharide-activated human blood, triflusal, aspirin, and HTB, but not sodium salicylate, inhibited COX-2-mediated prostaglandin E2 (PGE2) production (IC50 = 0.16, 0.18, 0.39, and >10 mM, respectively). However, only triflusal and aspirin inhibited purified COX-2 enzyme. To test this apparent discrepancy, we realized that HTB and triflusal (but neither aspirin nor salicylate) produced a concentration-dependent inhibition of COX-2 protein expression in peripheral human mononuclear cells. This observation was further confirmed in a rat air pouch model in vivo, in which both aspirin and triflusal inhibited PGE2 production (ID50 = 18.9 and 11.4 mg/kg p.o., respectively) but only triflusal-treated animals showed a decrease in COX-2 expression. This different behavior may be, at least in part, due to the ability of HTB and triflusal to block the activation of the transcription factor nuclear factor-kappaB to a higher extent than aspirin and sodium salicylate. Thus, in addition to inhibiting the COX-2 activity at therapeutic concentrations, triflusal is able to block through its metabolite HTB the expression of new enzyme, and hence the resumption of PGE2 synthesis. Triflusal and HTB may exert beneficial effects in processes in which de novo COX-2 expression is involved and, in a broader sense, in pathological situations in which genes under nuclear factor-kappaB control are up-regulated.
Animals↗
[Inhibition of pump and permeability mechanisms].
The presence of multidrug efflux-pump systems in bacteria showing resistance to various drugs is increasingly reported in the literature. These systems are inducible by compounds such as salicylate and can thus be involved in situations of phenotypic resistance at the point of the infection which would otherwise be barely detectable under standard laboratory testing conditions. On the other hand, mutants which overproduce efflux-pumps and show increased levels of antibiotic resistance are easily selectable. It has been shown that inactivation of efflux-pump determinants produces an increased susceptibility to different antibiotics as well as prevents the emergence of mutants with a high-level antibiotic resistance to drugs such as quinolones. The search for efflux-pump inhibitors to be used in combination with other currently used antibiotics is therefore an important task for the renewal of the antibacterial therapeutic armamentarium. No efflux-pump inhibitors are commercially available as yet. However, several companies are in the process of working on their development. In this review, we discuss four possible targets that could be useful in the screening of inhibitors of efflux-pump systems in bacteria.
Bacteria↗
The effect of proteolytic enzymes on hair follicles of transgenic mice expressing the lac Z-protein in cells of the bulge region.
OBJECTIVE: To study the effects of proteolytic enzymes on mice hair follicles, particularly on cells of the bulge area regarded as follicle stem cells. BACKGROUND: Previous application by iontophoresis of proteolytic enzymes on guinea pig skin resulted in degenerative effects on hair follicles and the hypothesis was proposed that some of the affected cells could be stem cells. METHODS: To mark putative stem cells transgenic mice were produced carrying the lac-Z gene fused to the Upstream Regulatory Region (URR) of Human Papilloma Virus 11 (HPV11), as they express this gene specifically in the cells of the bulge area. Chymotrypsin and papain were applied on skin by iontophoresis, trypsin in the form of liposomes. RESULTS: Enzyme application, both by electrophoresis and as liposomes, led to intense degenerative effects of the hair follicle, such as detachment of the inner root sheath, cystic dilation of the hair shaft and presence of epithelial cells within the lumen. Some of these cells represent hair follicle stem cells expressing beta-galactosidase (beta-gal), having been detached from the bulge area as a result of enzyme treatment, implying impairment of their function.
Animals↗