PubMed Health⌕ Search

Biomedical subjects

J M Escola

Publications and source records attributed to J M Escola.

12 recordsLinked to original sources
PubMed2005

Hyperhomocysteinemia in patients with mild chronic renal failure.

BACKGROUND: The aim of this study was to evaluate the prevalence of high plasma levels of homocysteine in patients with mild renal failure. METHODS: Forty-six chronic renal failure patients (25 males and 21 females, mean age 55.6+/-14.4 years) were recruited for the study. Mean plasma creatinine was 2.1+/-1.0 mg/dl and mean creatinine clearance was 50.6+/-26.3 ml/min. Patients with severe renal failure were excluded. Patients were compared with a control group with normal renal function (n=35, 22 men and 13 women, mean age 50.0+/-11.5 years). Plasma homocysteine values were measured in both groups at baseline and after an oral overload of methionine. RESULTS: Baseline homocysteine levels of patients were higher than those of controls (16.5+/-7.3 vs. 10.4+/-4.2 micromol/l, p<0.0001). Some 34 patients and 4 controls had increased plasma homocysteine levels at baseline. After the oral overload, 4 more patients had abnormally increased homocysteine levels, meaning that 83% of the patients with chronic renal failure had hyperhomocysteinemia. CONCLUSIONS: Hyperhomocysteinemia is a very common finding among patients with mild renal failure. The need for vitamin supplementation should be evaluated in the first stage of chronic renal failure.

Journal Article↗
PubMed2001

Antigen loading of MHC class I molecules in the endocytic tract.

Major histocompatibility complex (MHC) class I molecules bind antigenic peptides that are translocated from the cytosol into the endoplasmic reticulum by the transporter associated with antigen processing. MHC class I loading independent of this transporter also exists and involves peptides derived from exogenously acquired antigens. Thus far, a detailed characterization of the intracellular compartments involved in this pathway is lacking. In the present study, we have used the model system in which peptides derived from measles virus protein F are presented to cytotoxic T cells by B-lymphoblastoid cells that lack the peptide transporter. Inhibition of T cell activation by the lysosomotropic drug ammoniumchloride indicated that endocytic compartments were involved in the class I presentation of this antigen. Using immunoelectron microscopy, we demonstrate that class I molecules and virus protein F co-localized in multivesicular endosomes and lysosomes. Surprisingly, these compartments expressed high levels of class II molecules, and further characterization identified them as MHC class II compartments. In addition, we show that class I molecules co-localized with class II molecules on purified exosomes, the internal vesicles of multivesicular endosomes that are secreted upon fusion of these endosomes with the plasma membrane. Finally, dendritic cells, crucial for the induction of primary immune responses, also displayed class I in endosomes and on exosomes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

The steroidogenic acute regulatory protein homolog MLN64, a late endosomal cholesterol-binding protein.

MLN64 is a transmembrane protein that shares homology with the cholesterol binding domain (START domain) of the steroidogenic acute regulatory protein. The steroidogenic acute regulatory protein is located in the inner membrane of mitochondria, where it facilitates cholesterol import into the mitochondria. Crystallographic analysis showed that the START domain of MLN64 is a cholesterol-binding domain. The present work was undertaken to determine which step of the intracellular cholesterol pathway MLN64 participates in. Using immunocytofluorescence, MLN64 colocalizes with LBPA, a lipid found specifically in late endosomes. Electron microscopy indicates that MLN64 is restricted to the limiting membrane of late endosomes. Microinjection or endocytosis of specific antibodies shows that the START domain of MLN64 is cytoplasmic. Deletion and mutagenesis experiments demonstrate that the amino-terminal part of MLN64 is responsible for its addressing. Although this domain does not contain conventional dileucine- or tyrosine-based targeting signals, we show that a dileucine motif (Leu(66)-Leu(67)) and a tyrosine residue (Tyr(89)) are critical for the targeting or the proper folding of the molecule. Finally, MLN64 colocalizes with cholesterol and Niemann Pick C1 protein in late endosomes. However, complementation assays show that MLN64 is not involved in the Niemann Pick C2 disease which, results in cholesterol lysosomal accumulation. Together, our results show that MLN64 plays a role at the surface of the late endosomes, where it might shuttle cholesterol from the limiting membrane to cytoplasmic acceptor(s).

Animals↗
PubMed1999

[Reduction in the rates of restenosis after coronary angioplasty with simvastatin and probucol].

INTRODUCTION AND OBJECTIVES: The restenosis rates after coronary angioplasty persist as an important problem even though multiple drug therapies and different devices have been tried. The reduction of the cholesterol and low density lipoproteins levels (and their oxidation) have proved to have a beneficial effect on atherosclerosis evolution. Both the lipid lowering and antioxidant agents have caused a reduction in the neointimal formation generated with the angioplasty balloon in animals, and their combination to improve endothelial dysfunction in humans. The aim of the present study is to prove whether the whole administration of two potent agents such as simvastatin and probucol, which reduce the lipid levels and their oxidation, are able to lessen the restenosis related process. PATIENTS AND METHODS: Thirty five consecutive patients with coronary angioplasty with no stent to whom 20 mg simvastatin and 500 mg probucol bid were given (group-A) were studied in a prospective non-randomized study. They were compared to a historic group of 40 patients under the standard treatment (group-B). Both groups were angiographically evaluated to determine the restenosis percentage. A lipid profile was performed on group-A patients. RESULTS: The restenosis occurred in 4 (11.4%) in group-A and in 17 (42.5%) in group-B patients and in 4 (10.0%) and 18 (39.1%) lesions respectively (p < 0.01). A new PTCA was performed on 2 (5.7%) group-A patients vs 13 (32.5%) in group-B (p < 0.01). There was a reduction in residual stenosis (34.2 +/- 19.7% vs 48.8 +/- 23.5%, p < 0.01) and a greater minimum luminal diameter (1.76 +/- 0.59 vs 1.46 +/- 0.70 mm, p < 0.05) in group-A than in group-B patients. CONCLUSIONS: Although studies with more patients are required, a combined lipid lowering and antioxidant therapy could achieve a reduction in angioplasty coronary restenosis.

Aged↗
PubMed1998

Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes.

Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82. Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs. In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-2, were mainly localized to the limiting membrane and were hardly detectable on the internal membranes of MIICs nor on exosomes. Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.

Antigens, CD↗
PubMed1998

[Treatment with pravastatin of dyslipidemia associated with diabetic nephropathy].

OBJECTIVE: Patients with type II diabetes mellitus have an increased risk of coronary he disease. We investigated the efficacy and safety of pravastatin in the treatment of patients with diabetic nephropathy and hypercholesterolemia. METHOD: In this 6-months study, 12 patients (4 men, 8 women, mean age 60.5 +/- 10.8 years), with diabetic nephropathy and hypercholesterolemia (fasting plasma low-density lipoprotein cholesterol levels -LDL-C- > 130 mg/dl) received pravastatin 10 mg/day. The dose could be doubled after 4 weeks. Seven patients have chronic renal failure. RESULTS: Significant reductions in LDL-C (-19.1%, p < 0.05), total cholesterol (-16%, p < 0.01), very-low-density lipoprotein cholesterol (-29.2%, p < 0.05), apolipoprotein B (-21.5%, p < 0.05), and triglycerides (-26.0%, p < 0.01) were noted. No changes were found either in high-density-cholesterol or its fractions (HDL2 and HDL3) or in apolipoprotein A plasmatic levels. Pravastatin was well tolerated and no one side effect was detected. No clinically significant changes on the control of diabetes, renal function, as assessed by plasmatic creatinin and creatinin clearance, and proteinuria were seen during the follow-up time. CONCLUSIONS: The results of the study demonstrate that pravastatin is well tolerated and effective in lowering total cholesterol and LDL-C in patients with diabetic nephropathy and hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1996

Characterization of a lysozyme-major histocompatibility complex class II molecule-loading compartment as a specialized recycling endosome in murine B lymphocytes.

We have previously identified an intracellular compartment involved in the association between processed lysozyme and IAk major histocompatibility complex class II molecules (called the lysozyme-loading compartment (LLC)). Here, we show that the LLC polypeptide composition analyzed by two-dimensional gel electrophoresis shares similarities with that of early endosomes, but not with that of late endosomes. The transferrin receptor, a well known marker for both early and recycling endosomes, colocalizes with IAk molecules in LLC. Moreover, both transferrin and fluid-phase markers have access to LLC after 15 min of internalization. In the presence of concanamycin B, SDS-stable dimer formation and transport of class II molecules out of LLC are impaired. In contrast, nocodazole treatment has no effect. These results suggest that LLC is a specialized compartment of the recycling pathway involved in lysozyme loading and in the targeting of lysozyme-major histocompatibility class II complexes toward the cell surface.

Animals↗
PubMed1996

HLA-DR4 and HLA-DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70-kD heat shock proteins.

Most patients with rheumatoid arthritis express particular HLA-DR alleles. The DRbeta1 chains of these alleles share a highly homologous amino acid motif, in their third hypervariable (HV3) region, and this motif seems to help the development of rheumatoid arthritis via unknown mechanisms. In an attempt to identify a ligand of this motif, we screened bacterial proteins. HV3 peptides from HLA-DRB1 alleles containing a QKRAA or RRRAA motif bound the 70-kD heat shock protein (HSP) from Escherichia coli, dnaK. In lymphoblastoid cells homozygous for these same HLA-DRB1 alleles the constitutive 70-kD HSP, HSP73, that targets selected proteins to lysosomes coprecipitated with HLA-DR. Thus the QKRAA and RRRAA amino acid motifs of HLA-DR mediate binding of HLA-DR to HSP73. This property may influence the intracellular route, processing or peptide associations of the HLA-DRbeta1 chain in these two rheumatoid arthritis-associated alleles.

Alleles↗
PubMed1995

Invariant chain induces a delayed transport from early to late endosomes.

Invariant chain associated with class II molecules is proteolytically processed in several distinct intermediates during its transport through the endocytic pathway. Using subcellular fractionation, early and late endosomal compartments were separated in human fibroblasts transfected with HLA-DR (4N5 cells) and supertransfected with invariant chain (4N5Ii cells) or invariant chain lacking most of the cytoplasmic tail (4N5 delta 20Ii cells). Early and late endosome membrane fractions were characterized by morphology and by analyzing the presence of the Rab5 and Rab7 GTPases as markers of early and late endosomes, respectively. The transfer of endocytosed horseradish peroxidase from early to late endosomes proceeded relatively rapid both in 4N5 and 4N5 delta 20Ii cells (t1/2 = 25 min), whereas this transfer was significantly delayed (t1/2 = 2 h) in 4N5Ii cells. Pulse-chase experiments showed that invariant chain and its degradation products were first observed in early endosomes and thereafter in late endosomes. Our results strongly suggest that invariant chain induces a retention mechanism in the endocytic pathway.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1995

Different endocytic compartments are involved in the tight association of class II molecules with processed hen egg lysozyme and ribonuclease A in B cells.

The processing of exogenous antigens and the association of peptides with class II molecules both occur within the endocytic pathway. 2A4 B lymphoma cells of the H-2k haplotype were grown in the presence or the absence of two different exogenous antigens (hen egg lysozyme and ribonuclease A) internalized by fluid-phase endocytosis. Using subcellular fractionation techniques, we demonstrate that, in the presence of hen egg lysozyme, newly synthesized SDS-stable class II molecules are detected in a dense endocytic compartment which does not have the characteristics of neither early and late endosomes nor lysosomes. In contrast, no SDS-stable class II molecules are observed between ribonuclease A and newly synthesized class II molecules. Interestingly, when class II molecules are analyzed at steady state, SDS-stable class II molecules induced by ribonuclease A are found in a compartment cosedimenting with late endosomes. These results suggest that the tight associations between ribonuclease A or hen egg lysozyme with class II molecules occur in distinct endocytic compartments and that these associations may depend on the sensitivity of antigens to proteolysis.

Animals↗
PubMed1994

The O-chain of Brucella abortus lipopolysaccharide induces SDS-resistant MHC class II molecules in mouse B cells.

LPS is the most important antigen of Brucella bacteria which are gram-negative facultative intracellular pathogens infecting a large proportion of animals and humans in the world. In order to get insights into the immune response mechanisms monitored by Brucella, its LPS was used as a model antigen. S-LPS, R-LPS, lipid A and O-chain purified from Brucella abortus were tested in their capacity of inducing SDS-resistant MHC class II molecules after incubation with murine B lymphoma cells. S-LPS and O-chain gave a significant response suggesting that O-chain might induce an association with class II itself or might act as a carrier for antigens to bind MHC class II molecules.

Animals↗