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Biomedical subjects

M Martí

Publications and source records attributed to M Martí.

At least 19 recordsLinked to original sources

Metastatic lymph node ratio as a prognostic factor in gastric cancer.

BACKGROUND: There is an association between the number of resected lymph node and the number of metastatic lymph nodes in gastric cancer, suggesting that pN category could be influenced by the extension of the lymphadenectomy. This study evaluates this association and proposes a comprehensive use of the ratio as prognostic factor. METHOD: Review of 183 consecutive patients with gastric adenocarcinoma. The association between the number of resected lymph nodes and the number of metastatic lymph nodes was analysed and evaluated with other prognostic factors. RESULTS: The number of lymph node metastases increased with the number of resected lymph nodes. The lymph node ratio was a better prognostic factor than the number of metastatic lymph nodes. CONCLUSIONS: The metastatic lymph node ratio seems to be a good prognostic factor, but needs further evaluation.

Adenocarcinoma↗

[Psychological features and Doppler-Duplex in erectile disfunction].

OBJECTIVES: To establish a relationship between Doppler-Duplex colour ultrasound after prostaglandin intracorporeal injec tion and psychological features in patients suffering from erectile dysfunction. METHODS: Forty two patients with erectile dysfunction were prospectively evaluated with Doppler-Duplex colour ultra sonography after intracavernosal injection of 20 micrograms of E1 prostaglandin. Dynamic vascular pattern were analyzed an penile tumescence were graded in poor, moderate or good (I, II, III). All of them completed the International Index of Erectile Dysfunction, International Exam of Personality Traits (IPDE) and the Symptom Checklist (SCL-90). RESULTS: 29 patients (69.05%) showed a normal ultrasonography response (Peak Systolic Velocity >30 cm/s; Telediastolic velocity negative or less than 5 cm/s and penile tumescence grade III) and were classified as good responders with probably psy chogenic erectile dysfunction. Patients who did not show these values were classified in the group of erectile dysfunction of vas cular origin. We found significative differences between the two groups in sex desire, tumescence and paranoid personality. Th more frequent personality features were paranoid and squizoid (excentric) and ananchastic and anxious (fearful ones). Somatization and obsessive-compulsive symptoms have been outlined over the rest. We have found that paranoid personality is sixteen times more frequent in patients with normal ultrasonography. CONCLUSIONS: Psychological features and dysfunctional personality traits accompany psychogenic and organic erectile dys function, thus it is thought that mixed aetiology coexist in this patients. Doppler-Dupplex Colour ultrasound is an usefu method to exclude organic vascular factors. On de basis of our article, is more common to find psychological discomfort an dysfunctional personality traits in patients with normal ultrasound, which may help in their diagnosis and treatment.

Adult↗

[Education and occupational social class: their relationship as indicators of socio-economic position to study social inequalities in health using health interview surveys].

AIM: To analyse the relationship between social class based on occupation and level of education in the study of social inequalities in health and use of health services. DESSIGN: Cross-sectional study (health interview survey). SETTING: General population of the city of Cornellà de Llobregat (Spain). PARTICIPANTS: Representative sample of subjects aged 14 years old or over (1043 men and 1101 women) who personally answered the questionnaire. MEASUREMENTS: We analyse the association between social class and level of studies and different independent variables (self-perceived health, smoking, medical visits) by means of logistic regression. RESULTS: The proportion of men who declare their self-perceived health as poor is higher among those who have low education (45.4%) than among those who have primary education level or higher (25.9%). The prevalence of smoking shows a similar pattern (54.2% versus 41.5%), with a gradient effect, which is statistically non-significant. However, these differences are no longer evident if social class is used to group the individuals. No clear association is observed between the use of health services and socio economic level. CONCLUSIONS: We need to use several indicators of socioeconomic position to evaluate social inequalities In this disadvantaged population, level of education seems to be a good indicator to study social inequalities in health.

Cross-Sectional Studies↗

[Conservative surgery of ovarian torsion in pediatrics].

The authors describe the case of two girls diagnosed of ovarian torsion secondary to a cyst. They were operated on by conservative ovarian therapy regardless the time of evolution and ovary macroscopical aspect. These 2 patients were 9 and 13 years old, with abdominal colic pain of 48 and 36 hours of evolution. The diagnosis by doppler sonography was ovarian torsion, with a 4 cms cyst in the right ovary in the first case and a 5 cms cyst in the left ovary in the second patient. Both patients were operated on. After untwisting the ovary, we instille warm saline solution to this ovary and, after waiting for 10 minutes, we resect the ovarian cyst and it recuperates partial and heterogeneous its pink colour. We advise to the family about the possibility of surgical reintervention if the ovary is not viable. After 10 and 12 days of surgical intervention, the Doppler sonography has confirmed the existence of ovary flow and the symmetry of affected ovary in comparation to the opposite on. At the present, both patients are asymptomatic, with exhaustive ultrasound controls. Ovarian torsion is the most frequent complication of ovarian tumours of pediatrics (3-16%) and this is a real emergency in gynecology. Traditionally, it has been recommended the exeresis of ovarian torsion. Regardless the blue aspect of isquemic ovary affected by torsion and the time of evolution, in our experience when there is a minimal possibility of ovarian viability, it is possible to follow a conservative therapy because the macroscopical aspect of the ovary is not necessarily related with the following evolution of the case.

Adolescent↗

The Cys-67 residue of HLA-B27 influences cell surface stability, peptide specificity, and T-cell antigen presentation.

Cys-67 of HLA-B27 is located in the B pocket, which determines peptide-binding specificity. We analyzed effects of the Cys-67 --> Ser mutation on cell surface expression, peptide specificity, and T-cell recognition of HLA-B*2705. Surface expression was assessed with antibodies recognizing either native or unfolded HLA proteins. Whereas native B*2705 molecules predominated over unfolded ones, this ratio was reversed in the mutant, suggesting lower stability. Comparison of B*2705- and Cys-67 --> Ser-bound peptides revealed that the mutant failed to bind approximately 15% of the B*2705 ligands, while binding as many novel ones. Two peptides with Gln-2 found in both B*2705 and Cys-67 --> Ser are the first demonstration of natural B*2705 ligands lacking Arg-2. Other effects of the mutation on peptide specificity were: 1) average molecular mass of natural ligands higher than for B*2705, 2) bias against small residues at peptide position (P) 1, and 3) increased P2 permissiveness. The results suggest that the Cys-67 --> Ser mutation weakens B pocket interactions, leading to decreased stability of the mutant-peptide complexes. This may be partially compensated by interactions involving bulky P1 residues. The effect of the mutation on allorecognition was consistent with that on peptide specificity. Our results may aid understanding of the pathogenetic role of HLA-B27 in spondyloarthropathy.

Amino Acid Substitution↗

Large sharing of T-cell epitopes and natural ligands between HLA-B27 subtypes (B*2702 and B*2705) associated with spondyloarthritis.

HLA-B*2702 is an ankylosing spondylitis-associated allotype that differs from the more common B*2705 at residues 77, 80, and 81, in the peptide-binding site. The diversity and fine specificity of alloreactive cytolytic T-lymphocyte (CTL) raised against B*2702 were analyzed at the clonal level. Significant crossreaction with B*2705 and B*2709 indicated that the three subtypes share numerous T-cell epitopes. However, some epitopes shared by B*2702 and B*2705 were lost in B*2709, which correlates with weaker association of this subtype to disease. Clonal specificities were donor-dependent, indicating that allo-immunogenicity is variable among individuals. Anti-B*2702 CTL were little affected by single mutations mimicking B*2702/B*2705 polymorphism, but the double mutant at positions 77 and 81 was recognized worse than B*2705, suggesting a compensatory effect of residue 80. Thus, HLA-B27 polymorphism modulated alloreactivity through cooperative and compensatory effects on T-cell epitope structure. Comparison of B*2705- and B*2702-bound peptide repertoires revealed that they overlapped by 73% and 81%, respectively. This was larger than B*2702/B*2705 cross-reaction, indicating that HLA-B27 allospecificity is only partially determined by the nature of peptide repertoires. The large sharing of natural ligands and T-cell epitopes is consistent with a pathogenetic role of B*2702 and B*2705 in spondyloarthritis based on antigen presentation.

Antigen Presentation↗

Confocal scanning laser microscopy examination of bovine vaginal fluid at oestrus.

This article reports the study of the structural elements of bovine vaginal fluid at oestrus using a confocal scanning laser microscope (CSLM) to examine samples collected from 10 lactating cows at the time of insemination. The filamentous glycoproteins, which form the structural component of vaginal fluid, were stained with fluorophore acridine orange for 10 min. This microscopy technique permits visualization of a network of non-oriented filaments of different thickness in a three-dimensional array. This arrangement was repeated throughout the sample and was common to all samples. Interfilament spaces varied in width between cows and ranged from 1 to 20 microns. The present results provide a new, non-aggressive technique for the study of biological samples that show hydrogel-like behaviour. Due to its simplicity, the CSLM technique proposed offers the advantages of (1) providing realistic images of vaginal fluid structure, free from artifacts arising from sample preparation, and (2) the possibility of observing specimens shortly after collection. CSLM proved to be a useful tool for the examination of vaginal fluid and may also serve as a good control for artifacts associated with scanning electron microscopy procedures.

Animals↗

Glutaryl-CoA dehydrogenase deficiency in Spain: evidence of two groups of patients, genetically, and biochemically distinct.

Glutaryl-CoA dehydrogenase (GCDH) deficiency causes glutaric aciduria type I (GA I), an inborn error of metabolism that is characterized clinically by dystonia and dyskinesia and pathologically by neural degeneration of the caudate and putamen. Studies of metabolite excretion allowed us to categorize 43 GA I Spanish patients into two groups: group 1 (26 patients), those presenting with high excretion of both glutarate and 3-hydroxyglutarate, and group 2 (17 patients), those who might not be detected by routine urine organic acid analysis because glutarate might be normal and 3-hydroxyglutarate only slightly higher than controls. Single-strand conformation polymorphism (SSCP) screening and sequence analysis of the 11 exons and the corresponding intron boundaries of the GCDH gene allowed us to identify 13 novel and 10 previously described mutations. The most frequent mutations in group 1 were A293T and R402W with an allele frequency of 30% and 28%, respectively. These two mutations were also found in group 2, but always in heterozygosity, in particular in combination with mutations V400M or R227P. Interestingly, mutations V400M and R227P were only found in group 2, and at least one of these mutations was found in 11 of 15 unrelated alleles, accounting together for 53% of the mutant alleles in group 2. Therefore, it seems clear that two genetically and biochemically distinct groups of patients exist. The severity of the clinical phenotype seems to be closely linked to the development of encephalopathic crises rather than to residual enzyme activity or genotype. Comparison of GCDH protein with other acyl-CoA dehydrogenases (whose x-ray crystal structure has been determined) reveals that most of the mutations identified in GCDH protein seem to affect folding and tetramerization, as has been described for a number of mutations affecting mitochondrial beta-oxidation acyl-CoA dehydrogenases.

Alleles↗

High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis.

HLA-B*2705 is strongly associated with ankylosing spondylitis (AS) and reactive arthritis. In contrast, B*2709 has been reported to be more weakly or not associated to AS. These two molecules differ by a single amino acid change: aspartic acid in B*2705 or histidine in B*2709 at position 116. In this study, we analyzed the degree of T cell epitope sharing between the two subtypes. Ten allospecific T cell clones raised against B*2705, 10 clones raised against B*2703 but cross-reactive with B*2705, and 10 clones raised against B*2709 were examined for their capacity to lyse B*2705 and B*2709 target cells. The anti-B*2705 and anti-B*2703 CTL were peptide dependent as demonstrated by their failure to lyse TAP-deficient B*2705-T2 transfectant cells. Eight of the anti-B*2705 and five of the anti-B*2703 CTL clones lysed B*2709 targets. The degree of cross-reaction between B*2705 and B*2709 was donor dependent. In addition, the effect of the B*2709 mutation (D116H) on allorecognition was smaller than the effect of the other naturally occurring subtype change at this position, D116Y. These results demonstrate that B*2705 and B*2709 are the antigenically closest HLA-B27 subtypes. Because allospecific T cell recognition is peptide dependent, our results imply that the B*2705- and B*2709-bound peptide repertoires are largely overlapping. Thus, to the extent to which linkage of HLA-B27 with AS is related to the peptide-presenting properties of this molecule, our results would imply that peptides within a relatively small fraction of the HLA-B27-bound peptide repertoire influence susceptibility to this disease.

Alleles↗

A molecular insight on the association of HLA-B27 with spondyloarthropathies.

This article focuses on molecular studies concerning HLA-B27 and their relevance for its pathogenetic role in spondyloarthropathy. The peptide binding and T-cell antigen presenting properties of HLA-B27 are discussed, mainly in connection with differential subtype association to ankylosing spondylitis. Molecular studies in transgenic rodents are also considered, with an emphasis on their relevance to the various pathogenetic mechanisms. Recent studies on the putative role of HLA-B27 in bacteria-host interactions are also discussed, as they suggest another level of implication of HLA-B27 in disease whose molecular basis is obscure.

Animals↗

HLA-DM can partially replace the invariant chain for HLA-DR transport and surface expression in transfected endocrine epithelial cells.

The function of HLA class II molecules as peptide presenters to CD4+ T cells depends on the expression of associated molecules such as the invariant chain (Ii) and DM responsible for the correct transport of and high-stability peptide binding to the class II dimers. In organs affected by autoimmune diseases, endocrine epithelial cells express class II molecules, which presumably are involved in the presentation of self-peptides to autoreactive T cells. We have transfected the rat insulinoma cell line RINm5F with different combinations of HLA-DR, Ii and HLA-DM cDNAs and have studied how Ii and DM affect the transport and stability of class II molecules expressed by the different transfectants. Immunofluorescence and biochemical analysis showed that cells transfected with DR and DM in the absence of Ii expressed mostly stable molecules in their surface, and showed a lower accumulation of DR molecules in the endoplasmic reticulum (ER) than cells expressing only DR. This suggests that, in the absence of invariant chain, DM molecules can not only exchange peptides other than class II-associated invariant chain peptide (CLIP) but may also be involved in the transport of class II molecules out of the ER towards the endosomal route. In addition, these data confirm that expression of DR alone or DR+Ii do not allow the formation of sodium dodecyl sulphate (SDS)-stable complexes, that cells expressing DR+Ii have most DR molecules occupied by CLIP and that Ii and DM molecules allow regular routing and peptide loading of class II molecules.

Animals↗

Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation.

Clinical transplantation of human islets has a disappointingly low rate of success. We report here the identification of a possible causative factor: endotoxin present in the collagenase preparations used to disperse the pancreatic tissue before islet purification and transplantation. Supporting evidence includes (1) detection of unexpectedly high levels of endotoxin in most collagenase solutions currently used to digest human pancreases; (2) demonstration that supernatants generated during islet separation are able to induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF-alpha in the islets during the separation procedure. Cytokine expression was assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha, confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin and locally induced cytokines carried over with the graft activate the endothelium and promote lymphomonocytic infiltration of grafted islets and surrounding liver tissue favoring primary nonfunction and early rejection. These results also have implications for the numerous experimental procedures that use collagenase, and they point to possible ways to improve islet preparation and transplantation protocols.

Adolescent↗

Plasma membrane and cytocortex alterations in frozen/thawed mouse embryos deprived of the zona pellucida.

We analyzed the morphological and ultrastructural abnormalities present in two-cell mouse embryos frozen/thawed without the zona pellucida (ZP). Transmission electron microscopy revealed that these embryos had plasma membrane abnormalities that were not observed in the embryos frozen/thawed with an intact ZP. The most frequent anomalies were a decreased number of microvilli with a nonhomogeneous distribution and showing an abnormal morphology and the presence of an increased number of vesicles in the periphery of the cell. The distribution of actin filaments, studied by fluorescence microscopy revealed alterations in both embryos, frozen/ thawed with ZP and embryos frozen/thawed without ZP: an increased staining in some regions of the peripheral actin band, discontinuities or gaps in the band, or the presence of a second actin band connected to the peripheral one.

Actins↗

An unusual late-onset case of propionic acidaemia: biochemical investigations, neuroradiological findings and mutation analysis.

UNLABELLED: We report a 5-year-old boy with propionic acidaemia who developed a rapidly fatal necrosis of the basal ganglia after an episode of clinical deterioration. Neither metabolic acidosis nor hyperammonaemia were present. Organic acid analysis in both urine and CSF showed increased levels of methylcitric and 3-hydroxypropionic acids. Propionic acidaemia was confirmed by demonstrating a propionyl-CoA carboxylase deficiency (11% of control value) in skin fibroblasts. DNA analysis revealed that the patient was a compound heterozygote for two mutations in the PCCB gene. CONCLUSION: Propionic acidaemia can present as a sudden and fatal neurological disease and not only as an organic aciduria with severe biochemical dis-turbances and progressive neurological deterioration.

Amino Acid Metabolism, Inborn Errors↗

[West's syndrome associated with inversion duplication of chromosome 15].

We describe a five year old boy with inversion duplication of chromosome 15 (inv dup (15)) who, at the age of six months had started to develop West's syndrome. He later developed cryptogenic myoclonic epilepsy which was resistant to medication. On examination there was dysmorphia, overall hypotonia and diffuse pyramidalism. On starting ACTH the crises of flexion spasms were reduced but these were soon followed by myoclonic crises, both tonic and atonic, which did not respond to the various anticonvulsive treatments given. We comment on the changes in chromosome 15 linked to convulsions, and particularly the phenotypes of the inv dup (15) which depend on the size and genetic composition of the anomaly. This is the third case described in the literature of a patient with West's syndrome associated with supernumerary inversion duplication of chromosome 15. It is suggested that the karyotype be included when studying convulsive encephalopathies and cryptogenic refractory epilepsy, especially in infantile spasms.

Child, Preschool↗

Characteristics of actin fibers and ultrastructure of the contact regions involved in the separation of blastomeres of two-cell mouse embryos, frozen-thawed without the zona pellucida.

Freezing of embryos deprived of the zona pellucida (ZP) decreases their survival rate immediately after thawing, and gives rise to the separation of their blastomeres in a high percentage of cases. We have studied the ultrastructure and the characteristics of actin fibers in the cell-to-cell contact region in mouse embryos frozen-thawed without the ZP at the two-cell stage. Our results indicate that most of the embryos that retain their blastomeres united after freezing and thawing show either the presence of a midbody, or a contact region with a close apposition of the plasma membranes but without an organized actin cortex in their contact region. Only a small percentage of embryos that retain their blastomeres united after freezing and thawing show a contact region with widely separated plasma membranes and an organized actin cytocortex.

Actins↗

Manual nucleofragmentation and endothelial cell loss.

PURPOSE: To compare corneal endothelial cell loss with two cataract surgery techniques: manual nucleofragmentation performed with the Keener nucleus divider and planned extracapsular extraction. SETTING: Department of Ophthalmology "Memorial Cristóbal Garrigosa," Hospital de l'Esperança, Universitat Autònoma de Barcelona, Spain. METHODS: Contact specular microscopy was performed before and 8 weeks after surgery in 51 patients who had been prospectively randomized into 2 groups: 26 patients had manual nucleofragmentation (NF) with the Keener divider and 25, planned extracapsular cataract extraction (ECCE). The analyzed parameters were preoperative and postoperative endothelial cell density and variations in cell size (polymegethism) and cell shape (pleomorphism). The results were compared and statistically analyzed. RESULTS: The mean percentage of endothelial cell loss in the NF group was 11.08% and in the ECCE group, 9.86%. This difference was not statistically significant. Postoperative variation in cell shape and size did not differ significantly between the two groups and was fairly constant. CONCLUSION: The percentage of endothelial cell loss that occurred with manual NF using the Keener nucleus divider was similar to the one that occurs with other cataract surgery techniques. The small variation detected in postoperative endothelial morphology suggests that this endothelial cell population is stable.

Aged↗