msJAMA: human rights violations and refugee health.
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Delivery of Health Care↗
Biomedical subjects
A Moreno
Publications and source records attributed to A Moreno.
Aortocardiac fistulas complicating infective endocarditis.
This study sought to determine the clinical and echocardiographic features, surgical approach, and outcome of patients with infective endocarditis complicated with aortocardiac fistulas among a series of 346 consecutive cases between 1988 and 1998. Nine patients (2%) were found to have aortocardiac fistulas complicating infective endocarditis caused by highly pyogenic pathogens (4 patients had ruptured abscesses of the right sinus of Valsalva, 3 had fistulous communications from the left coronary sinus, and 1 had a fistulized abscess in the noncoronary sinus). Mortality in these patients was very high (55%), even when surgery was attempted early in the course of the disease and reconstructive procedures were implemented.
Adult↗
Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells.
Tumoral lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) are long-lived cells in vivo, but they die rapidly by apoptosis in vitro. Here, it is reported that endothelial cells (ECs) inhibit the apoptosis of B-CLL cells, as determined by 4 different flow cytometric methods, and that this antiapoptotic effect is mediated mainly by soluble factor(s), as can be deduced from the following findings. First, EC-conditioned medium (ECCM) inhibited the apoptotic rate in B-CLL to approximately 50% of control. Second, the antiapoptotic effect mediated by EC/B-CLL cell contact was more apparent than real; using a fluorescence-based phagocytosis assay, it was demonstrated that this effect was due to the phagocytic capacity of ECs, which internalized apoptotic cells. Third, the protective effect of ECCM was associated neither with proliferation nor differentiation signals. Fourth, the survival factor was a dimeric form of IL-6 because anti-IL-6 antibodies completely neutralized the antiapoptotic effect mediated not only by the crude ECCM but also by the 45- to 55-kd active fractions obtained after gel filtration, which contained high levels of IL-6. These IL-6 dimers (IL-6(D)) were noncovalently associated. Sixth, human recombinant IL-6(D) (hrIL-6(D)) inhibited B-CLL apoptosis, whereas hrIL-6 monomers (hrIL-6(M)) did not. Binding and functional competition experiments showed not only that monomers and dimers had similar affinity for the IL-6R, but also that hrIL-6(M) inhibited the antiapoptotic activity of hrIL-6(D). These data suggest that IL-6(D) derived from ECs promote the survival of B-CLL cells.
Annexin A5↗
Cathepsin C gene: First compound heterozygous patient with Papillon-Lefèvre syndrome and a novel symptomless mutation.
Papillon-Lefèvre syndrome (PLS) has recently been shown to be caused by mutations in the cathepsin C gene resulting in periodontal disease and palmoplantar keratosis. Thirteen different homozygous mutations have been characterised in PLS patients of different ethnic origin. In the present paper, a PLS patient is described who carries two novel mutations (706G>T and 872G>A) in the paternal and maternal chromosomes, respectively. This is the first compound patient described so far. In addition, a novel symptomless mutation (458C>T) in the cathepsin C gene is described in three homozygous individuals. Thus, not all mutations should be considered as a cause of disease, whether case studies or general population screening is performed. Another already described mutation that provoked the Haim-Munk syndrome (HMS) in Indian Jews has also been found to give rise to PLS in a Spanish family from Madrid. On the other hand, PLS patients are ameliorated by retinoids, which indicates that retinoids may be used as therapeutic agents in this immune system deficiency.
Alleles↗
Alternative 1-(13)C glucose infusion protocols for clinical (13)C MRS examinations of the brain.
Clinical utility of (13)C MRS is limited by cost and long examination times. Three 1-(13)C glucose infusion protocols-a high-dose i.v., low-dose i.v., and oral administration of 1-(13)C glucose-were compared on a GE 1.5T MR scanner. Resolution and sensitivity were sufficient to identify (13)C glucose (1alpha and 1beta), glutamate (C1-C4), glutamine (C1-C4), aspartate (C2 and C3), lactate, alanine, and bicarbonate in brain spectra. The three protocols were efficacious, as measured by cerebral enrichment of 1-(13)C glucose (62%, 42%, and 38%) and its principal metabolite, 4-(13)C glutamate (13%, 11%, and 16%), respectively. Intravenous infusion of 1-(13)C glucose 0.23 g/kg body weight (low dose) provides equivalent information at one third the cost of previous regimes. Magn Reson Med 46:39-48, 2001.
Administration, Oral↗
1-(13)C glucose magnetic resonance spectroscopy of pediatric and adult brain disorders.
With protocols designed for use in a clinical environment we investigated the feasibility and diagnostic potential of (13)C MRS after 1-(13)C labeled glucose infusion. (13)C MRS brain examinations were performed in 27 subjects (17 children and pediatric patients, six adult patients, and four adult controls), using a standard 1.5 T clinical MR scanner. 1-(13)C glucose, 99% enriched (20% w/v) was administered intravenously (690 or 210 mg/kg body weight) or orally (730 mg/kg). Cerebral (13)C-enrichment patterns and time courses were compared. 1-(13)C glucose appeared in brain spectra within 2.5-15 min, with ensuing enrichment of its metabolites. No complications were encountered. When data obtained in patients were compared with controls, striking abnormalities in hepatic encephalopathy and in premature brain were observed, consistent with reduced cerebral glucose metabolism. Abnormalities in the (13)C enrichment pattern were also observed in pediatric patients with leukodystrophies and mitochondrial disorders. In this preliminary survey, we conclude that (13)C MRS in combination with glucose infusion is safe and efficient and provides new insights into the pathophysiology of brain disorders.
Adolescent↗
Flow cytometry, a useful tool for detecting the lethal effect of pentamidine on Leishmania viannia complex promastigote forms.
Flow cytometry (FC), combined with propidium iodide as supravital colorant, was used to study Leishmania(subgenus Viannia)panamensis [L (V) panamensis] complex strain susceptibility to meglumine antimoniate, sodium stibogluconate and pentamidine. Despite all drugs examined being leishmanicidal to axenic forms in in vitro trials (in the presence of macrophages), axenic amastigotes directly exposed to these drugs were highly resistant under our experimental conditions. A direct lethal effect on promastigotes, detectable by FC, was only obtained with pentamidine after in vitro treatment of both promastigotes and axenic amastigotes with the drugs. Pentamidine's rapid lethal effect, as detected by FC, could be further confirmed in short- and long-term parasite cultures after exposure to a drug. FC's suitability for measuring L (V) panamensis complex's promastigote susceptibility to pentamidine, shortly after in vitro drug exposure, might be useful in monitoring clinical trials with this drug and facilitating rapid pentamidine-resistant natural isolate identification.
Animals↗
Management of biliary duct confluence injuries produced by hepatic hydatidosis.
From 1978 to 1999 a total of 850 patients underwent surgical treatment for hydatid disease of the liver at our surgical department. Biliary duct confluence injuries produced by hepatic hydatidosis (HH) were founded in six patients (0.7%). Surgical intervention was undertaken to relieve the obstructive jaundice and clinical manifestations of cholangitis and to treat the hydatid cyst. A partially open cystopericystectomy technique was used in three patients with a double bilioenteric Roux-en-Y reconstruction. The remaining three patients (two with prehepatic portal hypertension and one with triple hepatic duct confluence) were subjected to a cystojejunostomy. There were no hospital deaths. Two cases of anastomotic leakage following a high bilioenteric anastomosis occurred but did not require surgical treatment. During the follow-up (5-19 years) one patient suffered local recurrence of the hydatid disease 7 years after cystojejunostomy. The site of intrahepatic biliary and vascular involvement, the presence of biliary duct anomalies, and the presence of portal hypertension are decisive factors when choosing the "ideal" procedure for reconstruction. Conservative surgical approaches (partial cystectomy and cystojejunostomy) are the treatments of choice. Radical surgery is often a serious matter.
Adolescent↗
Influence of water hardness on the bioavailability and toxicity of linear alkylbenzene sulphonate (LAS).
In the present work, the influence of Ca2+ concentration on the toxicity of single cut linear alkylbenzene sulfonate (LAS) homologues was studied. Precipitation boundary diagrams for each homologue were obtained, indicating turbid and clear zones depending on the LAS and Ca2+ concentrations. The separation between transparent and turbid zones is given by the so-called precipitation line. LAS toxicity to Daphnia magna was determined at concentrations close to this precipitation line. It was observed that when Ca(LAS)2 precipitation progresses, LAS bioavailability decreases for test animals, and the toxicity diminishes even at high nominal LAS concentrations. According to the "free ion activity model" (FIAM), the toxicity of a given chemical compound is mainly due to the ionic species (Ca2+-LAS-) and not due to the precipitated molecule, Ca(LAS)2. The significance of the present study is in connection with the assessment of LAS sorption/precipitation studies in soils and sediments, where in situ toxicity is strongly influenced by Ca2+/Mg2+ ions, according to the results presented in this work.
Alkanesulfonic Acids↗
Microsatellite instability is associated with the loss of apoptosis in ductal breast carcinomas.
Metastatic progression in ductal breast carcinomas are related to apoptosis in primary tumors. Frameshift mutations in a single-repeat sequence within the coding region (G)8 of the pro-apoptotic Bax gene have been related to microsatellite instability (MSI) and progression of some carcinomas and lymphomas. The aim of this study was to explore whether the extended lifespan of breast cancer cells can also be triggered by Bax mutation in ductal-breast carcinomas, and whether breast cancer cell MSI is related to the loss of apoptosis. For this purpose we studied frameshift mutations of a microsatellite (G)8 in the third exon of the Bax gene in a series of 105 ductal breast carcinomas, at T1 and T2-3 stages, 45 of which had lymph node metastasis. We analyzed MSI in five sequences of DNA isolated from normal and tumor tissue samples taken from 86 patients, and we explored the relationship between MSI and tumor apoptosis status. Bax mutation was not present in ductal breast carcinomas. MSI (two or more markers altered) was detected in 11.6% of tumors. Loss of apoptosis occurred in 80% (8/10) tumors with MSI, versus 17.8% of tumors without MSI (chi2 test, p = 0.0004), independently of Bax protein expression. We conclude that frameshift mutations of a microsatellite (G)8 of the Bax gene are not critical for the loss of apoptosis in breast cancer, and that loss of apoptosis may be a consequence of overexpression of anti-apoptotic protein Bcl-2 or Bcl-xL. Moreover, MSI in breast carcinomas might be the cause of loss of an apoptotic pathway that is not induced by frameshift mutations of a microsatellite (G)8 of the Bax gene.
Adult↗
Amyloid beta-peptide promotes permeability transition pore in brain mitochondria.
In this work the effect of the neurotoxic amino acid sequence, Abeta25-35, on brain mitochondrial permeability transition pore (PTP) was studied. For the purpose, the mitochondrial transmembrane potential (deltapsim), mitochondrial respiration and the calcium fluxes were examined. It was observed that Abeta25-35, in the presence of Ca2+, decreased the deltapsim, the capacity of brain mitochondria to accumulate calcium and led to a complete uncoupling of the respiration. However, the reverse sequence of the peptide Abeta25-35 (Abeta35-25) did not promote the PTP. The alterations promoted by Abeta35-25 and/or Ca2+ could be reversed when Ca2 was removed by EGTA or when ADP plus oligomycin were present. The pretreatment with CsA or ADP plus oligomycin prevented the deltapsim drop and preserved the capacity of mitochondria to accumulate Ca2+. These results suggest that Abeta25-35 can promote the PTP induced by Ca2+.
Adenosine Diphosphate↗
Novel mutations and defective protein kinase C activation of T-lymphocytes in ataxia telangiectasia.
Three ataxia telangiectasia (AT) patients have been characterized immunologically and molecularly. Patient 1 presents two nondescribed splicing mutations which affect exons 15 and 21 of the ATM gene. The maternal defect consists of a G > A transition in the first nucleotide of the intron 21 donor splicing site which results in a complete deletion of exon 21. The paternal mutation consists of an A > C transversion in the intron 14 acceptor splicing site which produces a partial skipping of exon 15. Two abnormal alternative transcripts were found, respectively, 17 and 41 nucleotides shorter. Patient 2 presents a homozygous genomic deletion of 28 nucleotides in the last exon of the gene. This deletion changes the normal reading frame after residue 3003 of the protein and introduces a premature stop codon at residue 3008 that could originate a truncated ATM protein. Patient 3, a compound heterozygote, presents a defect which consists of a G > A transition in the first nucleotide of intron 62 donor splicing site which results in a complete deletion of exon 62. The results obtained during a three year period in the proliferation assays show an impaired PMA (phorbol myristate acetate) activation in specific T lymphocyte activation pathways (CD69, CD26, CD28, CD3, PHA, PWM and Con A mediated) but not in others (CD2, ionomycin, and Ig surface receptor). The possible link among specific ATM mutations and abnormal immune responses is unknown.
Ataxia Telangiectasia↗
Direct determination of the N-acetyl-L-aspartate synthesis rate in the human brain by (13)C MRS and [1-(13)C]glucose infusion.
A non-invasive (13)C magnetic resonance spectroscopy (MRS) technique is described for the determination of the N-acetyl-L-aspartate (NAA) synthesis rate, V(NAA), in the human brain in vivo. In controls, the mean V(NAA) was 9.2 +/- 3.9 nmol/min/g. In Canavan disease, where [NAA] is increased (p < 0.001) and [aspartate] is deceased (p < 0.001), V(NAA) was significantly reduced to 3.6 +/- 0.1 nmol/min/g (p < 0.001). These rates are in close agreement with the activity of the biosynthetic enzyme measured in vitro in animals, and with the rate of urinary excretion of NAA in human subjects with Canavan disease. The present result is consistent with the regulation of NAA synthesis by the activity of a single enzyme, L-aspartate-N-acetyltransferase, in vivo, and with its control in Canavan disease by limited substrate supply and/or product inhibition. The (13)C MRS technique provides the means for further determination of abnormal rates of neuronal NAA synthesis among neurological disorders in which low cerebral [NAA] has been identified.
Adult↗
Stimulation by thimerosal of histamine-induced Ca(2+) release in intact HeLa cells seen with aequorin targeted to the endoplasmic reticulum.
The oxidizing thiol reagent, thimerosal, has been shown to activate reversibly the inositol 1,4,5-trisphosphate (InsP(3)) receptor in several cell types. We have studied here the effects of thimerosal by monitoring the [Ca(2+)] inside the endoplasmic reticulum (ER) of intact HeLa cells with targeted aequorin. We show that thimerosal produced little effects on the ER-Ca(2+)-pump and only slightly increased the ER-Ca(2+)-leak in intact cells. Instead, thimerosal increased the sensitivity to histamine of ER-Ca(2+)-release by about two orders of magnitude, made the response much more prolonged at saturating histamine concentrations and enhanced both cytosolic and mitochondrial [Ca(2+)] responses to histamine. Moreover, inhibition of ER-Ca(2+)release by cytosolic [Ca(2+)] microdomains was fully preserved and sensitive to BAPTA-loading, and histamine-induced Ca(2+) release remained quantal in the presence of both thimerosal and intracellular BAPTA. The effects of thimerosal were reversible in the presence of dithiotreitol, suggesting the possible presence of a physiological redox regulatory mechanism. However, in permeabilized cells thimerosal potentiated InsP(3)-induced Ca(2+) release but oxidized glutathione had no effect. In addition, thimerosal increased the [Ca(2+)](ER) steady-state level in permeabilized cells. Thimerosal partially inhibited also plasma membrane Ca(2+)extrusion and increased Ca(2+)(Mn(2+)) entry through the plasma membrane, both phenomena contributing to increase the steady-state cytosolic [Ca(2+)]. Thimerosal-induced Ca(2+) entry was additive to that induced by emptying of the ER, suggesting that store-operated Ca(2+) channels may not be involved. These results provide new insights on the mechanisms of activation and inactivation of InsP(3) receptors.
Aequorin↗
First experience in Spain with MARS in three patients with advanced liver failure.
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Adult↗
Use of the DELI-microtest to determine the drug sensitivity of Plasmodium falciparum in Burkina Faso.
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Animals↗
Expression of CD61 (beta3 integrin subunit) on canine cells.
A monoclonal antibody (JM2E5) specific for the integrin beta3 chain, or CD61 or GPIIIa subunit, has been employed to determine the expression of the canine homologue CD41/CD61 or CD51/CD61 complex on different canine cells in peripheral blood lymphocytes, monocytes, granulocytes, platelets, erythrocytes, lymph-node cells, spleen cells and breast tumour cells). The canine homologue CD41/CD61 or CD51/61 was present on peripheral blood lymphocytes, monocytes, granulocytes, breast tumour cells and spleen cells as well as on platelets and it was absent from erythrocytes and lymph-node cells. An antigen with components of molecular masses of 25/100/120 kDa (under reducing conditions) was immunoprecipitated from canine peripheral lymphocytes and platelets, but not from granulocytes or monocytes. Expression on canine lymphocytes of the canine homologue of the human beta3 integrin chain was unexpected, based on the expression pattern of this molecule in human tissue.
Animals↗
Antiplatelet effects of prostacyclin and nitric oxide in patients with type I diabetes and ischemic or edematous retinopathy.
The aim of this study was investigate prostacyclin and nitric oxide (NO) and their platelet second messengers cAMP and cGMP, in patients with type I diabetes with or without retinopathy. We compared 20 healthy volunteers and 97 patients with type I diabetes: 24 with no signs of diabetic retinopathy (DR), 43 with ischemicproliferative DR, and 30 with edematous DR. The following parameters were recorded: platelet aggregometry, nitrites/nitrates, 6-keto-prostaglandin-F(1alpha), and intraplatelet cAMP and cGMP. Platelet aggregation was greater in patients with edematous DR. The platelets in patients with diabetes were more resistant to inhibition by prostaglandin E(1) or sodium nitropruside. Nitrite concentration in patients with ischemic-proliferative DR was 80% lower than the value in healthy controls, but there was no significant difference between the control group and patients with edematous DR. In the latter group, stimulation of neutrophils with L-arginine increased nitrite + nitrate production by 44 +/- 3.6%, whereas in patients with ischemic-proliferative DR, the increase was 9.8 +/- 0.8%. We conclude that NO production is higher in patients with type I diabetes and edematous retinopathy than in those with ischemic-proliferative retinopathy. This finding, together with the possibly greater production of free radicals, may explain the greater impairment of platelet function in the former patients.
Adult↗