PubMed Health⌕ Search

Biomedical subjects

A Giner

Publications and source records attributed to A Giner.

At least 19 recordsLinked to original sources
PubMed1999

Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13.

SNAREs and Rab GTPases cooperate in vesicle transport through a mechanism yet poorly understood. We now demonstrate that the Rab5 effectors EEA1 and Rabaptin-5/Rabex-5 exist on the membrane in high molecular weight oligomers, which also contain NSF. Oligomeric assembly is modulated by the ATPase activity of NSF. Syntaxin 13, the t-SNARE required for endosome fusion, is transiently incorporated into the large oligomers via direct interactions with EEA1. This interaction is required to drive fusion, since both dominant-negative EEA1 and synthetic peptides encoding the FYVE Zn2+ finger hinder the interaction and block fusion. We propose a novel mechanism whereby oligomeric EEA1 and NSF mediate the local activation of syntaxin 13 upon membrane tethering and, by analogy with viral fusion proteins, coordinate the assembly of a fusion pore.

Adenosine Triphosphatases↗
PubMed1998

Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells.

A key feature of polarized epithelial cells is the ability to maintain the specific biochemical composition of the apical and basolateral plasma membrane domains while selectively allowing transport of proteins and lipids from one pole to the opposite by transcytosis. The small GTPase, rab17, a member of the rab family of regulators of intracellular transport, is specifically induced during cell polarization in the developing kidney. We here examined its intracellular distribution and function in both nonpolarized and polarized cells. By confocal immunofluorescence microscopy, rab17 colocalized with internalized transferrin in the perinuclear recycling endosome of BHK-21 cells. In polarized Eph4 cells, rab17 associated with the apical recycling endosome that has been implicated in recycling and transcytosis. The localization of rab17, therefore, strengthens the proposed homology between this compartment and the recycling endosome of nonpolarized cells. Basolateral to apical transport of two membrane-bound markers, the transferrin receptor and the FcLR 5-27 chimeric receptor, was specifically increased in Eph4 cells expressing rab17 mutants defective in either GTP binding or hydrolysis. Furthermore, the mutant proteins stimulated apical recycling of FcLR 5-27. These results support a role for rab17 in regulating traffic through the apical recycling endosome, suggesting a function in polarized sorting in epithelial cells.

Amino Acid Sequence↗
PubMed1996

Relationship between immunoinflammatory proteins containing sialic acid and low-density lipoprotein serum concentrations.

The aim of this study was to investigate the relationship between sialoglycoproteins and the lipoprotein profile in a group of children with different levels of low-density lipoprotein cholesterol. We have studied 177 children of 132 families who were sent to our Pediatric Lipid Research Clinic because of serum cholesterol concentrations higher than 5.17 mmol/l. At the time of diagnosis, we analyzed the serum lipoprotein profile and the sialoglycoproteins: alpha 1-antitrypsin, acid alpha 1-glycoprotein, haptoglobin, alpha 2-macroglobulin, transferrin, IgA, IgG, IgM, complement C3 component and ceruloplasmin. At 7.0 to 10.9 years, alpha 1-glycoprotein serum concentrations were higher in the high risk group than in the moderate risk group (P < 0.05). At 2.0 to 6.9 years, IgA and IgM serum concentrations were higher in the moderate risk group than in the low risk group (P < 0.05 and P < 0.01, respectively), and IgG and IgM serum concentrations were also higher in the high risk group than in the low risk group (P < 0.05). Our results seems to reflect a general reaction to injury or inflammation which could be associated with the atherosclerotic process.

Adolescent↗
PubMed1995

A GDP/GTP exchange-stimulatory activity for the Rab5-RabGDI complex on clathrin-coated vesicles from bovine brain.

Small GTPases of the Rab family are key regulators of intracellular transport. They are associated with the cytoplasmic surface of distinct exocytic and endocytic organelles and with transport vesicles connecting these compartments. Rab proteins are also present in the cytosol in the GDP-bound conformation complexed to Rab GDP dissociation inhibitor (RabGDI). Upon membrane association, RabGDI is released, and the Rab protein is converted into the GTP-bound form. In this paper we have investigated whether Rab5, which regulates the clathrin-coated vesicle-mediated pathway of endocytosis, can directly associate with the membrane of clathrin-coated vesicles (CCV) purified from bovine brain in vitro. We found that RabGDI can specifically deliver Rab5 but not Rab7, which is localized to late endosomes, to CCV. Furthermore, CCV contain a heat- and trypsin-sensitive activity that stimulates the dissociation of GDP from Rab5, but not from Rab7, and the subsequent binding of GTP. The activity was found to be associated with the CCV membrane but not with the coat components. CCV weakly stimulated GDP release from either post-translationally modified or unmodified Rab5 alone. However, maximal GDP dissociation stimulation required the presence of RabGDI, suggesting that the factor(s) responsible for the membrane association and GDP/GTP exchange of Rab5 recognize the protein complexed to RabGDI. These data demonstrate that CCV are competent for acquiring Rab5 and for converting the molecule into the GTP-bound active form.

Animals↗
PubMed1995

Lymphocyte T subset counts in children with elevated low-density lipoprotein cholesterol levels.

The aim of this study was to determine blood lymphocyte T subset counts in children with elevated levels of low-density lipoprotein cholesterol. We studied 107 children, ages 2.0 to 15.9 years, from 79 families who were referred to our Lipid Research Clinic because total cholesterol serum levels higher than 200 mg/dl had been detected in at least one child. At the time of diagnosis we analyzed serum lipoprotein profile and blood lymphocyte T subsets (CD3, CD4 and CD8). Children were classified according to LDL-C levels into three groups: (1) normal, if levels were between the 5th and 75th percentiles (50 and 125 mg/dl, respectively); (2) at moderate risk, if levels were between the 75th and 95th percentiles (125 and 150 mg/dl, respectively); and (3) at high risk, if levels were above the 95th percentile (150 mg/dl). In children aged 2.0 to 6.9 years, all lymphocyte T subset counts were higher in the high risk group than in the normal group (P < 0.05 and P < 0.01). In children aged 11.0 to 15.9 years, the CD4 subset count was also significantly higher in the high risk group in the other two groups (P < 0.05 and P < 0.01). These results are in agreement with pathologic findings in the atheromatous plaque.

Adolescent↗
PubMed1993

Site-specific photocross-linking reveals that Sec61p and TRAM contact different regions of a membrane-inserted signal sequence.

A chemically charged amber suppressor tRNA was used to introduce the photoactivatable amino acid (Tmd)Phe at a selected position within the signal sequence of the secretory protein preprolactin. This allowed the interactions of the NH2-terminal, the central, and the COOH-terminal regions of the signal sequence to be investigated during insertion into the membrane of the endoplasmic reticulum (ER). We found that different regions of the nascent chains were photocross-linked to different ER proteins. The TRAM protein (translocating chain-associating membrane protein) contacts the NH2-terminal region of the signal sequence while the mammalian Sec61p contacts the hydrophobic core of the signal sequence and regions COOH-terminal of this. These results suggest that the ER translocation complex is composed of heterologous protein subunits which contact distinct regions of nascent polypeptides during their membrane insertion.

Acylation↗
PubMed1993

[Hematic parameters in chronic hypoxemia].

The hematic effects of hypoxia have been studied in 184 patients divided in four groups: 1) 10 patients with pO2 values in capillary blood lower than 43 mmHg; 2) 40 patients with pO2 between 43 and 50 mmHg; 3) 134 subjects with pO2 between 51 and 62 mmHg; and 4) 39 normal subjects (control). Hypoxemic subjects show higher erythrocyte concentrations than normoxemic ones, but without reaching the point of polycythemia and without significant differences in the hemoglobin concentration. The values of the mean corpuscular volume, the mean corpuscular hemoglobin and the concentration of the mean corpuscular hemoglobin show no significant differences between the groups. The amplitude of the red corpuscle distribution has not shown statistically significant differences between the groups of more pronounced hypoxia and those of slight hypoxia and control. The hematocrit, determined in the autoanalyzer, does not show any significant differences between the groups, whereas the one obtained by centrifugation is higher in the hypoxemic groups. Differences are non-significant in platelet count, mean platelet volume, and platelet distribution among the groups. The leucocyte count yields progressively higher values as blood pO2 decreases, with an accompanying increase in the percentage of neutrophyle granulocytes and a decrease in lymphocytes. Leucocytes with peroxidasic activity are significantly higher when the oxygen offer is lower.

Adult↗
PubMed1992

Signal-sequence recognition by an Escherichia coli ribonucleoprotein complex.

Hydrophobic signal-sequences direct the transfer of secretory proteins across the inner membrane of prokaryotes and the endoplasmic reticulum membranes of eukaryotes. In mammalian cells, signal-sequences are recognized by the 54K protein (M(r) 54,000) of the signal recognition particle (SRP) which is believed to hold the nascent chain in a translocation-competent conformation until it contacts the endoplasmic reticulum membrane. The SRP consists of a 7S RNA and six different polypeptides. The 7S RNA and the 54K signal-sequence-binding protein (SRP54) of mammalian SRP exhibit strong sequence similarity to the 4.5S RNA and P48 protein (Ffh) of Escherichia coli which form a ribonucleoprotein particle. Depletion of 4.5S RNA or overproduction of P48 causes the accumulation of the beta-lactamase precursor, although not of other secretory proteins. Whether 4.5S RNA and P48 are part of an SRP-like complex with a role in protein export is controversial. Here we show that the P48/4.5S RNA ribonucleoprotein complex interacts specifically with the signal sequence of a nascent secretory protein and therefore is a signal recognition particle.

Bacterial Proteins↗
PubMed1992

Tobacco, physical exercise and lipid profile.

A group of 572 young cadets from the General Military Academy in Zaragoza (AGEMZA) with a mean age of 19.9 years was studied in two different situations: on admission to the AGEMZA, when physical activity was very intensive (A) and after 8 months, by which time they had all received identical diets and physical activity was considerably reduced (B). On both occasions they were asked about their smoking habits and their personal and family histories. Their height and weight were recorded and a sample of venous blood was taken to determine the lipid, biochemical and haematological profiles. We found that more smokers had a family history of sudden death or acute myocardial infarction than the non-smokers. The smokers also showed a lower HDL cholesterol level (54.3 +/- 9.8 mg.dl-1 +/- SD) than the non-smokers (59.4 +/- 10.9) (P less than 0.0001) and a higher level of triglycerides (75.4 +/- 24.7 mg.dl-1) than the non-smokers (65.4 +/- 21.1 mg.dl-1). The smokers had a higher white cell count (8194 +/- 1981 vs 7332 +/- 1672 cells. 10mm-3) (P less than 0.001), a higher haemoglobin value (14.9 +/- 0.9 vs 14.6 +/- 0.9 g.dl-1) (P less than 0.004) and a higher haematocrit value (44.2 +/- 2.3 vs 43.6 +/- 2.7%) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

[Effect of physical training on hematological parameters in young swimmers].

PURPOSE: To evaluate the effects of a regular training programme on some haematological values in a group of young swimmers. MATERIAL AND METHODS: The study group is composed of 32 infantile swimmers (18 boys and 14 girls) and the control group of 12 boys and 11 girls of similar ages, performing no sports. Blood samples were taken at the beginning of training and four months later. Automated blood cell counts were performed in duplicate, along with assessment of the serum levels of iron, ferritin, transferrin and haptoglobin. The statistical study was made by comparison of means (Student's t, Wilcoxon and Mann-Whitney's U tests). RESULTS: Significant descent of haemoglobin rates (p < 0.05) was found in the swimmers, whereas serum iron was also significantly decreased (p < 0.01). Transferrin and haptoglobin were increased in both sexes (p < 0.01) in the swimmers, while ferritin was increased only in the female swimmers. With regard to the control groups, the boys showed significantly higher levels of ferritin both at the beginning and the end of the test, whereas the girls had lower only at the beginning (p < 0.01). CONCLUSIONS: After a 4-month physical training programme the tissular iron deposits are increased in a population of infantile swimmers, such increase being significant only in females.

Blood Proteins↗
PubMed1992

Serum enzymes activities at rest and after a marathon race.

With the purpose of determining the long and short term changes in serum enzyme activities after a marathon race, a survey involving nine healthy male runners was carried out. A basal blood sample was extracted from each 24 hours prior to the race and three further extractions were made immediately after the race, as well as at 1 and a final 24 h after the end of the race. In the enzymes of preferably hepatic origin--alkaline phosphatase (AP), ganna-glutamyltransferase (GGT) and alanine aminotransferase (ALT)--scanty modifications were found and these could be related to the changes observed in the plasma volume. Enzymes such as aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), which are widely distributed in the tissues, were found to have undergone more marked variations and these could not be related to the changes in the volume of the plasma, while in enzymes of muscular origin such as aldolase (ALD), creatine kinase (CK) and its cardiac isoenzyme (CK-MB), notable increases were observed due to the muscular injury suffered. The greatest example of this was the increase found in total CK 24 h after the end of the marathon (414.6%). The high serum percentages found in CK-MB in these endurance-trained runners in relation to total CK activity should be carefully assessed in order to avoid false diagnosis of acute myocardial infarction.

Adult↗
PubMed1990

E. coli 4.5S RNA is part of a ribonucleoprotein particle that has properties related to signal recognition particle.

E. coli 4.5S RNA and P48 have been shown to be homologous to SRP7S RNA and SRP54, respectively. Here we report that expression of human SRP7S in E. coli can suppress the lethality caused by depletion of 4.5S RNA. In E. coli, both RNAs are associated with P48. In vitro, both E. coli P48 and SRP54 specifically bind to 4.5S RNA. Strains depleted of 4.5S RNA strongly accumulate pre-beta-lactamase and fail to accumulate maltose binding protein. These effects commence well before any growth defect is observed and are suppressed by expression of human SRP7S. Strains overproducing P48 also accumulate pre-beta-lactamase. 4.5S RNA and P48 are components of a ribonucleoprotein particle that we propose to be required for the secretion of some proteins.

Cloning, Molecular↗
PubMed1989

Passive transfer of contact sensitivity to colophony as a complication of an allogenic bone-marrow transplant.

A 29-year-old woman developed allergic contact dermatitis from colophony 1 year after an allogenic bone-marrow transplant for refractory anaemia. The donor had a previous history of contact dermatitis from colophony, with a positive patch test. Although we cannot absolutely exclude active sensitization, it seems highly improbable because host immunity is severely restricted by the chemoradiotherapy used to prepare marrow graft recipients. The clinical data therefore suggest that sensitivity to colophony was passively acquired through marrow transplantation.

Adult↗