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Biomedical subjects

F García

Publications and source records attributed to F García.

At least 145 records · Page 8Linked to original sources
PubMed1994

T cell allorecognition and endogenous HLA-B27-bound peptides in a cell line with defective HLA-B27-restricted antigen presentation.

The B*2702+ lymphoblastoid cell line NW is unable to present at least some HLA-B27-restricted viral antigens to T cells. This defect was genetically inherited, and was suggested to be related to the nature of the HLA-B27 binding peptides reaching the endoplasmic reticulum in these cells (Pazmany et al., J. Exp. Med. 1992. 175: 361). In the present study 17 of 19 HLA-B27-specific alloreactive cytotoxic T lymphocyte clones recognizing the B*2702 subtype on other cells also lysed NW cells. Only two cytotoxic T lymphocyte clones failed to lyse NW while efficiently killing other B*2702+ cell lines. The high-performance liquid chromatography profiles of the B*2702+ bound peptides extracted from NW cells was similar, but not identical, to those from two other cell lines. These results indicate that the HLA-B27-bound peptide repertoire in NW cells is not fundamentally different from those in other B*2702+ cells. Our data argue against gross differences in peptide processing or transport as being responsible for the defective presentation of particular HLA-B27-restricted viral antigens to T cells, but do not rule out distinct presentation of some endogenous peptides. Differences in the capacity to present certain peptides could cause differential susceptibility among HLA-B27+ individuals to ankylosing spondylitis.

Antibodies, Monoclonal↗
PubMed1994

Structure of HLA-B27-specific T cell epitopes. Antigen presentation in B*2703 is limited mostly to a subset of the antigenic determinants on B*2705.

The structure of HLA-B27-specific epitopes recognized by anti-B*2705 and anti-B*2703 cytotoxic T lymphocytes (CTL) from three unrelated donors was examined with site-specific mutants at various side-chain pockets in the antigen-binding site. The effect of any given mutation on allorecognition correlated strongly with its predictable effect on peptide binding. Acidic charges in the C/F pocket of HLA-B27, which binds C-terminal peptide residues, strongly modulated allorecognition. Anti-B*2705 CTL from different donors were differently affected by some mutations, indicating individual differences in the structure of epitopes recognized by alloreactive CTL from each donor. Most anti-B*2703 CTL recognized a subset of epitopes that were also present on B*2705, but differed from the bulk of allospecific epitopes on this subtype in their smaller dependence on pocket A structure, where the difference between these subtypes is located, and in their greater dependence on Glu45, in the B pocket. The structure of the very few epitopes on B*2703 not shared by B*2705 was quite different from that of the much more predominant cross-reactive epitopes. The results strongly suggest that B*2703 is antigenically defective as compared with B*2705 and that this is due to the fact that the repertoire of peptides presented by B*2703 consists mainly of a subset of the B*2705-bound peptides which do not critically require the canonic binding of the peptidic N-terminus to a B*2705-like A pocket, because they are sufficiently stabilized by other contacts through the peptide binding site.

Antigen-Presenting Cells↗
PubMed1994

Histological study in contralateral testis of prepubertal children following unilateral testicular torsion.

Histological changes in the contralateral testis in 8 prepubertal children whose ages ranged from 3 to 7.5 years with a history of testicular torsion and subsequent atrophy were studied. The following histological parameters were evaluated: fertility tubular index (FTI), Sertoli cell index (SCI) and minimum tubular diameter (MTD). According to our findings and following Nistal and Paniagua's classification (1984) for tubular alterations, we found 5 cases (62.5%) who present the following alterations. Type 1 (case 2): FTI was decreased above 50% corresponding to slight germinal hypoplasia with normal MTD and SCI. Type 2 (cases 3 and 5): testis with remarkable germinal hypoplasia; FTI was between 30 and 50% while MTD was below normal values. Type 3 (case 8): testis with diffuse tubular hypoplasia; FTI was below 30%, whereas MTD showed 33% decrease regarding normal values. Type 4 (case 6): testes with hyperplasia of Sertoli cells; SCI was increased one third with regard to that corresponding to his age; FTI showed severe hypoplasia of germ cells. No relationship between alterations in either the age of the patients or the time elapsed since the torsion was observed. Because of all these facts and the young age of our patients, we believe that the alterations found in the contralateral testis were due to congenital dysgenesia.

Atrophy↗
PubMed1994

[High prevalence of hepatitis B and C markers in an indigent community in Caracas, Venezuela].

Hepatitis B and C serological markers were evaluated in indigent patients living in a workhouse in Caracas, Venezuela. Three out of 146 specimens were reactive for HBsAg (2.1%) and 41 for anti-HBc (28%). Eight sera were reactive for antibodies against HCV, and 7 were confirmed by immunoblot assays (4.8%). Four out of these 7 HCV-positive sera were also HCV-RNA positive. The prevalence for viral hepatitis markers was significantly higher than that found in blood donor population in Caracas. The probable risk factors associated with this high prevalence of blood-borne viral hepatitis were: promiscuity, transfusion, drug addiction, alcoholism and history of reclusion. This high prevalence of hepatitis B and C compels the precaution for medical and paramedical staff attending this kind of patients.

Adult↗
PubMed1994

Nasal CPAP during wakefulness increases intraocular pressure in glaucoma.

Few important side-effects of nasal continuous positive airway pressure (nCPAP) have been reported. No increase of intraocular pressure (IOP) complicating this treatment has previously been described. The goal of our study was to analyse the influence of nCPAP on IOP. We evaluated 18 patients previously diagnosed as having glaucoma and 22 normal subjects. nCPAP was used during wakefulness, at +12 cmH2O for 15 min. The results showed that nCPAP significantly increases IOP in patients with glaucoma (before nCPAP 20.3 +/- 6.3 mmHg) (mean +/- SEM); after nCPAP 22.3 +/- 5.7 mmHg. We believe that nCPAP might be relatively contraindicated in difficult to manage glaucoma patients, if these results are corroborated.

Female↗
PubMed1994

[Imported acute hepatitis in Spanish travelers to tropical countries].

Among the immunizable diseases, viral hepatitis is the most frequently diagnosed in travellers. The epidemiology and the clinical presentation of the imported viral hepatitis among patients in the Tropical Medicine Unit of Hospital Clínic (Barcelona) are studied in this article. A retrospective review of 47 viral hepatitis in Spanish travellers seen during the period 1988-1991 is presented, representing 2.47% of all diagnosis. Only a third of the patients were hepatitis A cases. The duration of the trip was significantly shorter in those who acquired hepatitis of the A and non-A--non-B types. Africa (60% cases), India and South East Asia (17%) and Central America (16%) were considered areas of risk. The B, C and non-A--non-B hepatitis types had a more silent clinical and biological presentation. Gathered data confirm the importance of hepatitis as an imported disease, the partial protection of the Spanish population against hepatitis A and the need to introduce this infection among the advice to be given in a travellers clinic.

Acute Disease↗
PubMed1994

Factors that influence the outcome of the intrauterine insemination with husband's sperm.

A retrospective analysis was undertaken in 160 intrauterine insemination with husband's sperm (IUIH) cycles, performed in 45 couples. The male factor represented the main indication (80%). Women who conceived had a lower duration of infertility (4.4 years +/- 3.0 vs 7.7 +/- 2.98). A significantly and pardoxically lower motility (3+ and 2+) was observed in raw specimens within conceptional cycles. However in prepared specimens in conceptional cycles the percentage of motility 3+ and 2+ was significantly increased (80.6% +/- 8.1 versus 70.7% +/- 20.2). The most significant difference was found in regard to a better response to preparation among conceptional cycles, expressed as the percentual increase in motility 3+ and 2+ (55.6% +/- 3.9 vs 41.3% +/- 19.4).

Adult↗
PubMed1993

[Prevalence of non-insulin dependent diabetes mellitus in Lejona (Vizcaya, Spain)].

BACKGROUND: Diabetes mellitus presents a high prevalence and morbimortality. The aim of the present study was to know the number of newly diagnosed diabetic patients in addition to those who present abnormal glucose tolerance and possible presence of associated risk factors. METHODS: This study was carried out in Lejona (Vizcaya) from 1984-1985. The prevalence of non insulin-dependent diabetes mellitus (NIDDM) and abnormal glucose tolerance (AGT) in people older than or equal to 30 years of age by a randomized sample stratified by pyramids of age and sex (n = 862). The following data were collected: age, sex, height, weight, medications taken, family and personal history of diabetes mellitus (DM) and blood pressure. A glycemia curve was made following the criteria recommended by the Committee of Experts of the World Health Organization (WHO). RESULTS: The prevalence of DM observed in the sample was of 6.4% (confidence interval of 95%: 4.75-8.01%) of which 3.6% corresponded to unknown DM and 2.8% to known DM. The prevalence of AGT was 10.4% (confidence interval 95%: 8.40-12.48%). Greater association was observed between DM and obesity, lower height, high blood pressure and age over 50. CONCLUSIONS: More than half of the diabetics were unaware of the disease. Given the association of non insulin-dependent diabetes mellitus with modifiable factors (obesity, high blood pressure) control of risk factors would be useful with the aim of decreasing the prevalence of diabetes mellitus and avoid the associated chronic complications of the disease.

Adult↗
PubMed1993

Effects of different factors in lead- and cadmium-induced hypothermia in mice.

The aim of this study was to investigate the relationship between the hypothermic effect induced by lead or cadmium chloride treatments and the cerebral metal levels attained. Mice were injected intraperitoneally with different doses of lead acetate or cadmium chloride at ambient temperatures of 22 degrees C and 35 degrees C, and rectal temperatures and brain metal levels were determined. At 22 degrees C, doses of lead acetate exceeding 25 mg/kg caused significant hypothermia and a rise of lead levels in the brain; this hypothermic effect was significantly inhibited at 35 degrees C. In mice repeatedly treated with 2 or 5 mg/kg lead acetate and exposed to 22 degrees C or 35 degrees C, no significant changes were observed in body temperature after the repeated exposure, although brain lead levels increased significantly. Cadmium chloride at 22 degrees C produced a significant fall in body temperature, and a rise in brain cadmium levels at doses of 2-4 mg/kg; the decrease in body temperature was partially inhibited at 35 degrees C. The results of the present study suggest that the hypothermic effect elicited by these heavy metals is related to both the level of metal absorbed by the brain and its rate of uptake.

Animals↗
PubMed1993

Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.

HLA-B27 subtypes share many structural features, including their pocket B, which interacts with a conserved Arg residue at the second position of B*2705-bound peptides. Subtypes differ among each other at other locations in the peptide binding site. In this study, metabolic labeling and radiochemical pool sequencing were used to address the following issues: (a) presence of the Arg 2 (R2) motif among peptides bound to the various HLA-B27 subtypes; (b) influence of mutations inside and outside pocket B on this motif; and (c) the degree of similarity among the peptide pools bound to the various B27 subtypes. Sequencing of Arg-labeled peptide pools extracted from B*2701 to B*2706, and from two site-directed mutants of B*2705 with changes outside pocket B, indicated that all of these molecules bind peptides with Arg at position 2. Peptides from several mutants with changes altering the structure of pocket B, and from one mutant at the pocket B rim, also retained the R2 motif. However, this was absent in the peptide pool extracted from the M45 mutant, in which the negative charge of pocket B, conferred to HLA-B27 by Glu45, was canceled. These results indicate that alterations outside pocket B, and even disruption of the network of hydrogen bonds that stabilizes Arg binding in pocket B, do not impair binding of peptides bearing the R2 motif, but a nonconservative substitution at position 45 does. As a substantial fraction of anti-B*2705 cytotoxic T lymphocyte (CTL) clones crossreact with the M45 mutant (Villadangos, J., B. Galocha, D. López, V. Calvo, and J. A. López de Castro. 1992. J. Immunol. 149:505) this result suggest that determinant mimicry by nonidentical peptides may frequently account for unexpected CTL crossreactions. Metabolic labeling with various other amino acids and radiochemical sequencing revealed similarities, but also substantial differences, among the peptide pools from the various HLA-B27 subtypes. This strongly suggests that many peptides bind to multiple subtypes, but significant subsets of peptides bound to a given HLA-B27 subtype do not bind to other subtypes or do so with greatly altered efficiency. These results indicate the importance of polymorphism outside pocket B in modulating peptide binding to HLA-B27.

Amino Acid Sequence↗
PubMed1993

Formation and characterization of cyclosporine-loaded nanoparticles.

The commercially available formulations of cyclosporine (cyclosporin A, CyA) are associated with acute hemodynamic changes that result in high nephrotoxicity. Among colloidal vectors, nanoparticles (NPs) are receiving much attention as potential drug carriers that would avoid the therapeutic risks of conventional formulations. Two different mechanisms for obtaining polymeric NPs loaded with CyA were studied with regard to their preparation and physicochemical characterization. Isobutyl-2-cyanoacrylate monomer (IBCA) was polymerized, whereas poly-E-caprolactone (PCL, a preformed polymer) was precipitated; both reactions took place in an aqueous medium containing Pluronic F-68 (polyoxypropylene polyoxyethylene block copolymer) as a surface active agent. The encapsulation efficiencies were 78.49 +/- 5.87 and 84.85 +/- 5.02%, respectively, and they remained stable over a wide range of drug concentrations. The polymeric NP had average sizes of 81 +/- 25 and 95 +/- 25 nm for poly-IBCA and PCL, respectively, as confirmed by photon correlation spectroscopy. Poly-IBCA NPs were built from oligomers with molecular weights of 157 to 2644 that joined to form a polymeric nanomatrix. In vitro activity of the drug and the carrier was tested by inhibition of lymphocyte proliferation induced by Concanavalin A. Drug-loaded PCL NPs and free CyA inhibited lymphocyte proliferation by 91.40 and 86.19%, respectively. However, drug-free NPs also exhibited statistically significant (p < 0.05) immunosuppressive activity.

Animals↗
PubMed1993

Diagnosis of HIV-1 infection by PCR with two primer pairs.

We have used two different primer pairs to assess HIV-1 infection of peripheral blood mononuclear cells (PBMC) by polymerase chain reaction (PCR). The study was carried out on 150 individuals: 50 seronegative individuals without risk behaviours for HIV-1 infection, 50 individuals with risk-behaviours but seronegative for HIV-1 and 50 patients with risk-behaviours who were HIV-1 seropositive. Discordances were found between the two primer pairs (SK38/39; SK68/69) in 3 cases. In the non-risk seronegative group, one specimen was scored positive with only one primer pair (SK38/SK39); all the samples belonging to seropositive individuals were found to be positive for HIV-1 DNA using both primer pairs; in the seronegative at risk group 2 samples were positive with only one primer pair (SK38/SK39), and 4 samples were found positive by both primer pairs (SK38/39 & SK68/69). Our study demonstrates that discrepant results take place with relatively high frequency; we propose that all specimens should be tested twice using at least two different primer pairs.

DNA Primers↗
PubMed1993

Kinetics of hypodermically injected technetium-99m and correlation with cutaneous structures: an experimental study in dogs.

We investigated the involvement of cutaneous structures in specific linear migration pathways of technetium-99m pertechnetate hypodermically injected at points of low electrical resistance in the metacarpus of male beagles. Skin-deep incisions were made in the front or back legs on either the same side as the 99mTc injection or on the opposite side. Incisions in the back legs did not affect the migration pattern. Incisions in the front legs before the injection of 99mTc prevented tracer migration. After the injection of 99mTc, incisions in the front contralateral leg caused sudden cessation of the migration, while incisions in the ipsilateral leg caused immediate disappearance of the pathway previously observed. Radioactivity was not detected in flaps obtained from the skin overlying the migration pathway or from the corresponding area of the contralateral leg. In conclusion, the specific linear migration pathways of 99mTc hypodermically injected at points of low electrical resistance cannot be explained by any known biological function. Although the migration of 99mTc does not seem to be strongly linked to any cutaneous structure, the skin overlying the radioactive pathway and the corresponding area of the contralateral leg must be intact if tracer migration is to take place.

Animals↗
PubMed1993

Serum hepatitis B virus DNA detection with S- and C-region-directed probes.

Developments in molecular biology have offered a wide range of nucleic acid probes to detect the genome of hepatitis B virus (HBV). We have tested the ability of two enzyme-linked (alkaline phosphatase) probes to detect HBV-DNA. These hybridise with the S and C regions of the genome of HBV and are used to determine the clinical significance of detecting the two regions. A total of 66 serum samples from patients at different stages of HBV infection was examined. HBV-DNA was detected with at least one of the probes in 17 (85%) patients with HBeAg-positive chronic hepatitis, five (26.3%) with anti-HBe-positive chronic hepatitis and six (66.6%) with acute hepatitis. Although both probes were able to detect as little as 10 pg/ml (2.86 x 10(6) g.E./ml) of a full length HBV-DNA standard, the C-region-directed probe did not react in one patient with acute hepatitis, two with HBeAg-positive and three with anti-HBe-positive chronic hepatitis. When C-region-directed probes are used for diagnostic purposes, results should always be accompanied by hybridisation with probes directed against other regions showing less variability (e.g. S region).

Acute Disease↗
PubMed1993

Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b: cloning, sequencing, and expression of the tyrosinase gene mepA.

Melanin production by Rhizobium meliloti GR4 is linked to nonsymbiotic plasmid pRmeGR4b (140 MDa). Transfer of this plasmid to GR4-cured derivatives or to Agrobacterium tumefaciens enables these bacteria to produce melanin. Sequence analysis of a 3.5-kb PstI fragment of plasmid pRmeGR4b has revealed the presence of a open reading frame 1,481-bp that codes for a protein whose sequence shows strong homology to two conserved regions involved in copper binding in tyrosinases and hemocyanins. In vitro-coupled transcription-translation experiments showed that this open reading frame codes for a 55-kDa polypeptide. Melanin production in GR4 is not under the control of the RpoN-NifA regulatory system, unlike that in R. leguminosarum bv. phaseoli 8002. The GR4 tyrosinase gene could be expressed in Escherichia coli under the control of the lacZ promoter. For avoiding confusion with mel genes (for melibiose), a change of the name of the previously reported mel genes of R. leguminosarum bv. phaseoli and other organisms to mep genes (for melanin production) is proposed.

Amino Acid Sequence↗