Biomedical subjects

L Gomes

Publications and source records attributed to L Gomes.

At least 19 recordsLinked to original sources

PubMed2003

Mode-locked ytterbium fiber laser tunable in the 980-1070-nm spectral range.

Spectral tuning of a mode-locked Yb-doped fiber laser over a 90-nm range is reported. Using semiconductor saturable absorber mirrors in a fiber laser cavity incorporating a grating-pair dispersive delay line, we obtain reliable self-starting mode locking over the whole tuning range. The wide tuning range is achieved by optimization of reflection characteristics and bandgap energy of the multiple-quantum-well semiconductor saturable absorber and by proper engineering of the laser cavity.

Journal Article↗

PubMed2003

Dipeptidyl peptidase IV (CD26) activity in the hematopoietic system: differences between the membrane-anchored and the released enzyme activity.

Dipeptidyl peptidase IV (DPP-IV; CD26) (EC 3.4.14.5) is a membrane-anchored ectoenzyme with N-terminal exopeptidase activity that preferentially cleaves X-Pro-dipeptides. It can also be spontaneously released to act in the extracellular environment or associated with the extracellular matrix. Many hematopoietic cytokines and chemokines contain DPP-IV-susceptible N-terminal sequences. We monitored DPP-IV expression and activity in murine bone marrow and liver stroma cells which sustain hematopoiesis, myeloid precursors, skin fibroblasts, and myoblasts. RT-PCR analysis showed that all these cells produced mRNA for DPP-IV. Partially purified protein reacted with a commercial antibody to CD26. The K M values for Gly-Pro-p-nitroanilide ranged from 0.43 to 0.98 mM for the membrane-associated enzyme of connective tissue stromas, and from 6.76 to 8.86 mM for the enzyme released from the membrane, corresponding to a ten-fold difference, but only a two-fold difference in K M was found in myoblasts. K M of the released soluble enzyme decreased in the presence of glycosaminoglycans, nonsulfated polysaccharide polymers (0.8-10 micro g/ml) or simple sugars (320-350 micro g/ml). Purified membrane lipid rafts contained nearly 3/4 of the total cell enzyme activity, whose K M was three-fold decreased as compared to the total cell membrane pool, indicating that, in the hematopoietic environment, DPP-IV activity is essentially located in the lipid rafts. This is compatible with membrane-associated events and direct cell-cell interactions, whilst the long-range activity depending upon soluble enzyme is less probable in view of the low affinity of this form.

Animals↗

PubMed2002

Mutational analysis of Portuguese families with multiple endocrine neoplasia type 1 reveals large germline deletions.

OBJECTIVE: To determine the spectrum of MEN1 mutations in Portuguese kindreds, and identify mutation-carriers. PATIENTS, DESIGN AND RESULTS: Six unrelated MEN1 families were studied for MEN1 gene mutations by single-strand conformational polymorphism (SSCP) and DNA sequence analysis of the coding region and exon-intron boundaries of the MEN1 gene. These methods identified 4 different heterozygous mutations in four families: two mutations are novel (mt 1539 delG and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and mt 1656 del C) all resulting in a premature stop codon. In the remaining two families, in whom no mutations or abnormal MEN1 transcripts were detected, segregation studies of the 5' intragenic marker D11S4946 and codon 418 polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene. Southern blot and tumour loss of heterozygosity analysis confirmed and refined the limits of these deletions, which spanned the MEN1 gene at least from: exon 7 to the 3' untranslated region, in one family, and the 5' polymorphic site D11S4946 to exon 9 (obliterating the initiation codon), in the other family. Twenty-six mutant-gene carriers were identified, 6 of which were asymptomatic. CONCLUSIONS: These results emphasize the importance of the detection of MEN1 germline deletions in patients who do not have mutations of the coding region. Important clues indicating the presence of such deletions may be obtained by segregation studies using the intragenic polymorphisms D11S4946 and at codon 418. The detection of these mutations will help in the genetic counselling of clinical management of the MEN1 families in Portugal.

Adolescent↗

PubMed2002

The distribution of structural neuropathology in pre-clinical Huntington's disease.

Putative neuroprotective agents in Huntington's disease may have particular application before brain pathology becomes manifest clinically. If these agents were to be tested in clinical trials, a reliable marker of the burden and rate of progression of pathological change in the pre-clinical group would be needed. The present study investigates whether the Huntington's disease genotype is associated with regional differences in brain structure, particularly differences that could not be predicted from clinical or neuropsychological assessment. A secondary aim is to seek indirect evidence of pathological progression in the form of changes in local tissue volume with age, specific to the Huntington's disease genotype. Formal motor examination, neuropsychological assessment, and T(1)-weighted cerebral MRI were performed in 34 subjects who had undergone predictive genetic testing for Huntington's disease. Clinical and cognitive testing were performed blinded to gene status. A linear discriminant analysis revealed the combination of test scores (the 'optimal clinical score') which best differentiated 18 subjects carrying the Huntington's disease gene mutation (the 'gene-positive' group). Voxel-based morphometry (VBM) was used to identify regions of significant main effect of Huntington's disease gene status on grey and white matter volume and regions of significant interaction of gene status with age. In the gene-positive group, there was significant reduction in grey matter volume in the left striatum, bilateral insula, dorsal midbrain and bilateral intra-parietal sulcus relative to 'gene-negative' controls. There was a significant reduction of periventricular white matter volume with age bilaterally in the gene-positive relative to the gene-negative group. Changes remained significant when controlled for differences in optimal clinical score between subjects. This study provides evidence of distributed grey matter pathology and progressive white matter atrophy with age before clinical onset of Huntington's disease. This suggests that VBM may be useful in monitoring cross-sectional and longitudinal changes in brain structure in pre-clinical Huntington's disease and for determining the efficacy of neuroprotective agents.

Adult↗

PubMed2002

Variations in the glycosaminoglycan content, swelling properties and morphological aspects of different regions of the superficial digital flexor tendon of pigs.

The superficial digital flexor tendon of pigs is a wrap around tendon supporting compressive in addition to the tensional forces in its proximal region, and only tensional forces in the intermediate region. Clear distinctions were observed in the physical properties, composition of proteoglycan and morphology for the different regions. A greater swelling in water and a larger amount of glycosaminoglycan were found in the proximal region compared to the intermediate one. Dermatan sulfate was detected in all regions of this tendon, while chondroitin sulfate was prominent only near the bone. In the toluidine blue stained sections, intense metachromasy was observed in the sites under compressive forces, especially in the portion close to the bone. Chondrocyte like cells were also observed in these arms. Crimp morphology, observed in the intermediate region, exhibited a clearly sloped aspect in relation to the main axis of the tendon. Elastic fibers were found in all regions, and were disposed in different directions in the areas under compressive forces, and parallel to the collagen bundles in the region under tension. These results reinforce the idea that mechanical forces contribute to a differentiated composition and organization of the extracellular matrix of tendons.

Animals↗

PubMed2001

Corpus callosum: microsurgical anatomy and MRI.

The anatomy of the corpus callosum has received renewed interest during recent years due to the increasing number of callosotomies performed to treat intraventricular lesions, as well as some forms of generalized epilepsy. We have previously reported on the microsurgical anatomy of the corpus callosum and identified specific anatomical reference landmarks that can be used during surgery. In the present study we have continued the anatomical aspect of this earlier work in a larger number of cases, with in vitro observations (brain out of skull) being compared with the corresponding in vivo features seen in sagittal MRI slices. Fifty-three in vitro microsurgical callosotomies was performed and the data collected compared with a series of 57 in vivo normal MR callosal images. Callosal dimensions were measured on both the anatomical and MRI material, thus overcoming the problems associated with in vitro callosal deformation. Of the anatomical landmarks studied the distance from the genu of the corpus callosum to the bifurcation of the columns of the fornix was found to be useful for the intraoperative evaluation of the extent of rostral callosotomy, as it is not significantly changed in in vitro. The main microsurgical features of rostral callosotomy are presented.

Adult↗

PubMed2001

Regional adaptations in three rat tendons.

Although detailed histological and immunocytochemical studies have been published for the rat calcanear tendon (CT), little is known of the structure, composition and biomechanics of the deep (DFT) and superficial (SFT) flexor tendons. In this study, we examined the structural specialization of these three tendons in 90-day-old rats by applying histochemical and biochemical assays to different tendon regions (proximal, intermediate and distal regions of the DFT and SFT, and proximal and distal regions of the CT). There were regional differences in tissue structure, glycosaminoglycan type and content, swelling properties and in the amount and distribution of elastic fibers. Dermatan sulfate occurred in all regions, but chondroitin sulfate predominated in the intermediate region of the DFT and in the distal region of the CT. These two chondroitin sulfate-bearing regions showed swelling in water, while all other regions lost fluid in water. Fibrocartilaginous sites were observed on the CT, one at the insertion to the bone and another distally at the innermost area of the tendon. The intermediate region of the DFT showed round cells disposed in lacunae, while the proximal and distal regions were typically fibrous. The intermediate region of the SFT showed a wavy array of collagen bundles but neither toluidine blue staining in the matrix nor round cells. Elastic fibers were present in each region of the three tendons, but were more prominent in the intermediate zone of the SFT. These results demonstrate regional variation in the three tendons. Tendon differentiation may occur by an increase in the number of elastic fibers and by variations in the arrangement of collagen fibers, without fibrocartilage formation.

Animals↗

PubMed2001

Transesophageal echocardiography in the assessment of patients presenting with ischemic cerebral events without previous evidence of a cardiac source of emboli.

UNLABELLED: Transesophageal echocardiography (TEE) is accepted as a valuable tool in the evaluation of ischemic stroke patients, particularly in the young and in cases of unknown cause. However, the real clinical impact of additional TEE data remains to be defined. PURPOSE: The aim of this study was to present our experience with TEE in ischemic stroke patients without previous evidence of a cardiac source of emboli. METHODS: From March 1991 to June 2000 we studied 172 patients (80 males, 92 females, mean age 43 +/- 12 years presenting with a transient ischemic attack or a recent cerebral infarction who had no previous evidence by clinical assessment, electrocardiogram and transthoracic echocardiography of a cardiac of emboli source. The population was divided into two groups: Group A--age < or = 45 years, n = 101 (43 males, 58 females, mean age 34 +/- 7 years) and Group B--age > 45 years, n = 71 (36 males, 35 females, mean age 54 +/- 7 years). Information was gathered from clinical records. In every case TEE included Doppler color flow imaging and multiple contrast injections (agitated saline) with and without Valsalva maneuver. RESULTS: A potential cardiac of emboli source was found in 29% of the patients, with a higher prevalence in the older group (group A--25%, Group B--35%, ns). Atrial septal abnormalities accounted for most of the detected findings (23 patent foramen ovale, 17 atrial septal aneurysms and two atrial septal defects, representing altogether 71% of the findings). The other detected anomalies were distributed as follows: aortic plaques--six, mitral valve prolapse--five vegetations--four, thrombus in left atrial appendage--two. Only six patients (3.5%) had abnormalities which in themselves determined a specific approach, which were found mostly in the older group (Group A--two vegetations; Group B--two vegetations, two thrombi). CONCLUSIONS: TEE identified additional findings with possible embolic potential in a considerable number of cases, the majority of which were of a debatable cause-effect relation. A higher diagnostic yield and clinical relevance was found in older patients, which argues against age being used as a selective criterion for it. Our experience suggests that routine TEE in this setting is of questionable value and has little impact on clinical management, for which reason TEE referral should be decided on an individual patient basis.

Brain Ischemia↗

PubMed2001

[Arterial blood pressure behavior during the administration of intravenous streptokinase, in patients with acute myocardial infarction].

OBJECTIVE: To evaluate the effect on blood pressure (BP) of intravenous (i.v.) streptokinase (SK) in patients (PTS) with acute myocardial infarction (AMI). DESIGN: Retrospective study with analysis of BP registers ten minutes before and during SK infusion. SETTING: PTS admitted to the Coronary Care Unit (CCU) of Santo António Hospital, Oporto. PATIENTS: Thirty-eight male PTS, average ages of 54, ranging from 38 to 67, AMI confirmed, and criteria to thrombolytic therapy. One patient was excluded on account of persistent hypotension since admission. MATERIAL AND METHODS: I.v. infusion of 1.500.000 U of SK over 60 minutes, preceded by 200 mg i.v. of prednisolone. BP and heart rate (HR) were evaluated with Datascope Accutorr 1A set. The lowest value of the systolic BP (SBP) recorded ten minutes before SK infusion was considered the baseline value. We valued the reduction of SBP above 15%, defining its fall as the difference between the baseline value and the minimum value of SBP recorded during the infusion. Hypertension was defined to SBP values below 90 mmHg. MAIN RESULTS: The fall was 40.4 +/- 22.1 mmHg (range 9 to 102, having been recorded the minimum value at 22.9 +/- 10.9 minutes. It was accompanied by diastolic BP (DBP) fall of 30.6 +/- 18.9 mmHg (range -2 to 76) and by a HR increasing from 76.2 +/- 13.7 beats/min. to 80.8 +/- 14.1 beats/min. (p < 0.01). In 86% of the PTS this fall was transient, lasting 8.9 +/- 6.3 minutes, and was corrected by slowing or stopping the infusion for a few minutes and placing the patient in Trendelenburg position. Two PTS needed sympaticomimetic amines because of persistent BP reduction despite the previous measures. 92% of the PTS had a SBP fall higher than 15% in relation to the baseline value. The SBP was kept over 90 mmHg in 20 PTS (54%); hypotension was recorded in the remaining 14 PTS (38%), and in 10 (27%) of these the SBP fell below 80 mmHg. We couldn't prove that the infarction and the extension of the ischemic lesion had influenced this BP fall. CONCLUSIONS: The BP reduction during treatment with high doses of SK deserves some attention because, although transient and easily reversible, it is frequent and sometimes significative. It demands then careful monitoring in order to avoid the hypoperfusion to the ischemic myocardium, that could jeopardize the potential benefits of reperfusion in the reduction of infarction area, the main objective of the thrombolytic treatment.

Adult↗

PubMed2000

Structure and proteoglycan composition of specialized regions of the elastic tendon of the chicken wing.

The elastic tendon of the avian wing has been described by others as a unique structure with elastic properties due to the predominance of elastic fibers in the midsubstance. Further analyses of the tendon have shown it to possess five anatomically distinct regions. Besides the major elastic region, a distally located fibrocartilage and three tendinous regions are present. The tendinous regions connect: (1) the muscle to the elastic region, (2) the elastic region to the fibrocartilage and (3) the latter to the insertion site. The elastic region possesses thick and abundant elastic fibers and very thin, interconnecting collagen fibers. The collagen fibers in the sesamoid fibrocartilage are thick and interwoven, defining spaces occupied by fibrochondrocytes embedded in a non-fibrillar and highly metachromatic matrix. Biochemical analyses have shown that the fibrocartilage has about tenfold the amount of glycosaminoglycans (GAGs) found in the other regions. The main GAG in this region was chondroitin sulfate (CS) (plus keratan sulfate as detected immunocytochemically), while the other regions showed variable amounts of CS, dermatan sulfate (DS) and heparan sulfate. Further analyses have shown that a large CS-bearing proteoglycan is found in the fibrocartilage. The elastic region possesses two main proteoglycans, a large CS-bearing proteoglycan (which reacted with an antibody against keratan sulfate after chondroitinase ABC treatment) and a predominant DS-bearing proteoglycan, which showed immunoreactivity when assayed with an anti-biglycan antibody. The results demonstrate that the elastic tendon is a complex structure with complex regional structural and compositional adaptations, suited to different biomechanical roles.

Animals↗

PubMed2000

Diaqua6,6'-dimethoxy-2,2'-

In the title compound, [Ni(C(19)H(20)N(2)O(4))(H(2)O)(2)], the Ni atom has a distorted octahedral coordination geometry in which the tetradentate Schiff base ligand acts as a cis-N(2)O(2) donor defining an equatorial plane, and water molecules occupy the axial positions. The two parts of the molecule are related by a mirror plane that passes through the Ni atom and is perpendicular to the equatorial plane. The angular distortions from normal octahedral geometry are in the range 1-6 degrees, and the equatorial plane, defined by the donor atoms of the Schiff base, is almost square planar. The six-membered ring comprising the Ni, the imine N and the propylene C atoms adopts a half-chair conformation. The Ni-O [2.017 (2) A] and Ni-N [2.071 (2) A] distances are within the ranges expected for high-spin octahedral nickel complexes.

Journal Article↗

PubMed2000

Multiple arterial anomalies in the newborn infant. Echocardiographic and angiographic diagnosis.

Multiple arterial anomalies characterized by tortuosity and rolling of the pulmonary arteries and aorta were diagnosed on echocardiography in an asymptomatic newborn infant with a phenotype suggesting Ehlers-Danlos syndrome. These changes were later confirmed on angiography, which also showed peripheral vascular abnormalities. The electrocardiogram showed a probable hemiblock of the left anterosuperior branch, and the chest x-ray showed an excavated pulmonary trunk with normal pulmonary flow.

Abnormalities, Multiple↗

PubMed2000

[Isolated infective endocarditis of pulmonary valve in patient with interventricular septal defect].

A case of isolated infective endocarditis of the pulmonary valve in a patient with known subpulmonary interventricular septal defect that had, as major complication pulmonary septic embolization, was reported by the authors. The disease followed an insidious course, diagnosed by the presence of vegetations in the echocardiogram, some of them larger than 1 cm. They were found in the right ventricular infundibulum and in the pulmonary valve leaflets. The isolation of Estreptococcus viridans in blood cultures has confirmed the diagnosis. In spite of appropriate antimicrobial therapy, according to the antibiogram data (with Ampicillin and Gentamicin), fever lasted for more than three weeks. This event suggested medical treatment failure and the possibility of surgery was considered. However, the endocarditis eventually healed with medical therapy alone, and this unusual course with prolonged fever was presumed to be caused by lung metastatic infection secondary to septic embolization. This complication is relatively common, but lung involvement is usually a subclinical event, not responsible for such persistent fever, as happened in the case now reported. We emphasize the rarity of this case, the unusual clinical course and the discussion concerning the therapeutic options.

Adult↗

PubMed2000

Binding of von Willebrand factor to collagen type III: role of specific amino acids in the collagen binding domain of vWF and effects of neighboring domains.

Binding of von Willebrand Factor (vWF) to sites of vascular injury is the first step of hemostasis. Collagen types I and III are important binding sites for vWF. We have previously determined the three-dimensional structure of the collagen binding A3 domain of vWF (Huizinga et al., Structure 1997; 5: 1147). We hypothesized that the top face of this domain might be the collagen-binding site. Based on this hypothesis, we made seven vWF mutants (D934A/S936A, V1040A/ V1042A, D1046A, D1066A, D1069A, D1069R, and R1074A). Collagen binding of these mutants was investigated in ELISA and with Surface Plasmon Resonance (BIAcore). In addition, we studied collagen binding of mutants lacking the A2 or D4 domains, which flank the A3 domain. In ELISA, all point mutants and deletion mutants bound to collagen in amounts similar to wild type (WT)-vWF. In the BIAcore we found that WT-vWF has an apparent KD for collagen of 1-7 nM on a subunit base. The apparent kinetic parameters of the point mutants and deletion mutants were not significantly different from WT-vWF, except for DA2-vWF, which had a lower KD. indicating that the A2 domain somehow modulates binding of vWF to collagen type III. Based on our results, we conclude that the amino acid residues mutated by us are not critically involved in the interaction between vWF and collagen type III, which suggests that the collagen binding site is not located on the top face of the A3 domain.

Binding Sites↗

PubMed1999

Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection.

Oxidative stress is suggested to be involved in several neurodegenerative diseases. One mechanism of oxidative damage is mediated by peroxynitrite, a neurotoxic reaction product of superoxide anion and nitric oxide. Expression of two cytokines and two key enzymes that are indicative of the presence of reactive oxygen intermediates and peroxynitrite was investigated in brain tissue of AIDS patients with and without AIDS dementia complex and HIV-seronegative controls. RNA expression of IL-1beta, IL-10, inducible nitric oxide synthase, and superoxide dismutase (SOD) was found to be significantly higher in demented compared with nondemented patients. Immunohistochemical analysis showed that SOD was expressed in CD68-positive microglial cells while inducible nitric oxide synthase was detected in glial fibrillary acidic protein (GFAP)-positive astrocytes and in equal amounts in microglial cells. Approximately 70% of the HIV p24-Ag-positive macrophages did express SOD, suggesting a direct HIV-induced intracellular event. HIV-1 infection of macrophages resulted in both increased superoxide anion production and elevated SOD mRNA levels, compared with uninfected macrophages. Finally, we show that nitrotyrosine, the footprint of peroxynitrite, was found more intense and frequent in brain sections of demented patients compared with nondemented patients. These results indicate that, as a result of simultaneous production of superoxide anion and nitric oxide, peroxynitrite may contribute to the neuropathogenesis of HIV-1 infection.

AIDS Dementia Complex↗

PubMed1999

Sialuria in a Portuguese girl: clinical, biochemical, and molecular characteristics.

Sialuria, a disorder of sialic acid (NeuAc) metabolism characterized by increased free NeuAc in the cytoplasm of cells, is due to failure of CMP-Neu5Ac to feedback inhibit UDP-N-acetylglucosamine (UDP-GlcNAc) 2-epimerase. We now describe the fifth patient in the world with sialuria, a 7-year-old Portuguese girl with developmental delay, hepatomegaly, coarse facies, and urinary excretion of 19 micromol of free NeuAc/mg creatinine. The patient's fibroblasts stored excess free NeuAc in the cytosolic fraction, and fibroblast UDP-GlcNAc 2-epimerase activity was only 26% inhibited by 100 microM CMP-Neu5Ac (normal, 79%). The patient's UDP-GlcNAc 2-epimerase gene displayed an R266Q mutation in only one allele, consistent with known sialuria mutations and with the proposed dominant nature of this disorder. Extensive description of sialuria patients will help to define the clinical and biochemical spectrum of this disease.

Abnormalities, Multiple↗

PubMed1998

Alterations in the growth and adhesion pattern of Vero cells induced by nutritional stress conditions.

The pattern of growth, adhesion and protein synthesis in Vero cells submitted to nutritional stress conditions was investigated. The control cells presented a characteristic pattern, with monolayer growth, while the stressed cells presented multilayered growth, with aggregate or spheroid formation which detached on the flask surface and continued their growth in another region. In the soft agar assay, with reduced amount of nutrients, only the stressed cells presented growth, indicating physical and nutritional independence. A 44-kDa protein was observed in stressed cells and was absent in non-stressed cells. The adhesion index and fibronectin synthesis and distribution were altered in stressed cells. After confluence, control cells presented fibronectin accumulation in lateral cell-cell contact regions, while this fibronectin accumulation pattern was not observed in stressed cells. These alterations may be responsible for the multilayered growth and decreased adhesion index observed in stressed cells which were transformed by nutritional stress conditions.

Animals↗

PubMed1998

A case of predominantly nocturnal soiling treated with amitriptyline.

The case of a 6 year old with soiling along with looseness of bowel and nocturnal soiling is reported. After failing to respond to conventional treatments, his symptoms remitted on a small dose of amitriptyline. Within the diversity of presentations of soiling, there may be a subgroup, not usually amenable to treatment, who can benefit from symptomatic treatment with tricyclic antidepressants.

Amitriptyline↗