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Biomedical subjects

I André

Publications and source records attributed to I André.

17 recordsLinked to original sources
PubMed2006

Streptococcal M protein: structural studies of the hypervariable region, free and bound to human C4BP.

Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an approximately 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of approximately 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.

Amino Acid Sequence↗
PubMed2000

Characterization of T cell precursor activity in the murine fetal thymus: evidence for an input of T cell precursors between days 12 and 14 of gestation.

In the mouse, the number and the differentiation potential of thymic migrants remain controversial. A fetal thymic organ culture under limiting dilution conditions allowed us to show a 130-fold increase in the numbers of T cell precursors in the embryonic thymus between days 12 and 14 of gestation. A comparative analysis of the most immature thymocytes at these two stages revealed that: (1) CD44(+)CD25(-) (DN1) thymocytes at 14 days post coitum (dpc) efficiently differentiate into mature T cells both in vivo and in vitro; (2) 12dpc thymocytes exhibit a low frequency of T cell precursors and were unable to generate a detectable progeny after in vivo intrathymic transfer. A 48-h organ culture of 12dpc thymic lobes did neither correct the low frequency of T cell precursors nor the absence of expression of T cell-specific genes observed in 12dpc thymocytes. We thus concluded that a fraction of recent thymic immigrants contribute to the observed properties in DN1 14dpc thymocytes. We show that increasing numbers of T cell precursors migrate to the thymus from 11 to 14 dpc. We propose that the first thymic immigrants do not contribute significantly to T cell generation which depends on the subsequent colonization by cells with a high T cell precursor potential.

Animals↗
PubMed1999

Different modes of pathogenesis in T-cell-dependent autoimmunity: clues from two TCR transgenic systems.

T lymphocytes constantly flirt with reactivity to self peptides, a price they pay for their ability to recognize foreign peptides presented by self-MHC molecules, and autoreactivity in the T compartment occasionally gives rise to autoimmune disease. Pathology from T-cell autoimmunity can manifest itself through radically different strategies, as we have observed recently in two transgenic models. In the BDC2.5 diabetes model, T cells express a transgene-encoded T-cell receptor (TCR) with reactivity against a pancreatic antigen. This leads to a massive, if often controlled, infiltration of the pancreatic islets. Target cell destruction then results from the local consequences of this local immune/inflammatory process. On the other hand, the arthritic manifestations of the KRN transgenic model are indirect: the transgenic TCR confers a broad autoreactivity, through which T cells stimulate B cells to produce arthritogenic immunoglobulins. These molecules are then sufficient to produce the disease, even in the complete absence of any lymphocytes. Although important questions subsist in this model--how the KRN T cells interfere with B-cell tolerance, what the target of arthritogenic IgG is--its implication is that an isolated T-cell dysregulation may manifest itself through an Ig-mediated disease.

Animals↗
PubMed1999

IgE multiple myeloma.

IgE multiple myeloma is a rare disease characterized by a high frequency of Bence-Jones proteinuria and plasma cell leukaemia when compared to other isotypes of monoclonal proteins. Only 35 cases have been reported. We describe a 70-year-old woman with a stage III IgE kappa multiple myeloma presenting with a sacral plasmacytoma. Immunological and biochemical studies showed IgE kappa producing tumoral plasma cells. Serum total IgE was high without clinical symptoms suggesting an hyperIgE syndrome or mast cell activation. The patient underwent surgical removal of the sacral tumor and monthly melphalan-prednisone treatment together with intravenous pamidronate infusions. Magnetic Resonance Imaging (MRI) of the dorsolumbar spine revealed an epidural process leading to T6-T9 radiotherapy. Bone densitometry showed a decreased bone mineral content supporting the management of myeloma-related osteoporosis with bisphosphonate infusions. A good partial response with plateau-phase and increase of bone mineral content was achieved after 1 year of treatment and still persists after a 28 months follow-up.

Aged↗
PubMed1997

Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes.

The role of interferon-gamma in autoimmune diabetes was assessed by breeding a null mutation of the interferon-gamma receptor alpha chain into the nonobese diabetic mouse strain, as well as into a simplified T cell receptor transgenic model of diabetes. In contrast to a previous report on abrogation of the interferon-gamma gene, mutation of the gene encoding its receptor led to drastic effects on disease in both mouse lines. Nonobese diabetic mice showed a marked inhibition of insulitis-both the kinetics and penetrance-and no signs of diabetes; the transgenic model exhibited near-normal insulitis, but this never evolved into diabetes, either spontaneously or after experimental provocation. This failure could not be explained by perturbations in the ratio of T helper cell phenotypes; rather, it reflected a defect in antigen-presenting cells or in the islet beta cell targets.

Animals↗
PubMed1996

Checkpoints in the progression of autoimmune disease: lessons from diabetes models.

In the last few years, data from experiments employing transgenic models of autoimmune disease have strengthened a particular concept of autoimmunity: disease results not so much from cracks in tolerance induction systems, leading to the generation of anti-self repertoire, as from the breakdown of secondary systems that keep these cells in check. T cells with anti-self specificities are readily found in disease-free individuals but ignore target tissues. This is also the case in some transgenic models, in spite of overwhelming numbers of autoreactive cells. In other instances, local infiltration and inflammation result, but they are well tolerated for long periods of time and do not terminally destroy target tissue. We review the possible molecular and cellular mechanisms that underlie these situations, with a particular emphasis on the destruction of pancreatic beta cells in transgenic models of insulin-dependent disease.

Animals↗
PubMed1996

Single crystals of inulin.

Lamellar crystals of inulin were grown by crystallizing sharp fractions of low molecular weight inulin from dilute aqueous ethanol solutions. The crystals were analyzed using three-dimensional electron diffraction and X-ray powder diagrams. Two crystalline polymorphs were observed, depending on the hydration conditions: a hydrated form which indexed on an orthorhombic unit cell, with space group P2(1)2(1)2(1) and with cell dimensions of a = 1.670 nm, b = 0.980 nm and c (chain axis) = 1.47 nm, together with a pseudo-hexagonal semi-hydrated form with unit cell parameters a = 1.670 nm, b = 0.965 nm and c (chain axis) = 1.44 nm. These parameters, together with the density data, indicate that inulin crystallizes along a pseudo-hexagonal six-fold symmetry with an advance per monomer of 0.24 nm. The difference between the hydrated and the semi-hydrated unit cells does not seem to correspond to any change in the conformation of inulin, but rather to a variation in water content.

Carbohydrate Conformation↗
PubMed1995

Conformation and dynamics of a cyclic (1-->2)-beta-D-glucan.

A molecular modelling and nuclear magnetic resonance spectroscopic study was performed in order to gain insight into the conformational preferences of cyclosophoroheptadecaose. MM3 molecular mechanics calculations predicted a non-symmetric conformer with a small cavity of 3.7 A diameter as the lowest energy form. Molecular dynamics simulations gave insight into the dynamics of the free cyclosophoroheptadecaose and also supported the results of molecular mechanics calculations. A fair agreement was found between experimental data and corresponding average values predicted by molecular modelling.

Carbohydrate Conformation↗
PubMed1989

[The clinical picture and development of aortic aneurysms in older persons].

The authors discuss 11 patients with aortal aneurysms (AA) which they diagnosed in the course of 1983-1988. In seven instances the abdominal aorta was affected; once the ascending part and once the arch; twice the descending part and once the whole aorta. In four patients the aneurysm had a dissecting character. Patients of advanced age were involved (73.9 +/- 9.7 years) with multiple morbidity and frequently also general advanced atherosclerosis which was the main cause of development of aneurysms. The authors analyze the clinical picture and course of AA in different patients and draw attention to their great variability. In the discussion they deal with the position of diagnostic methods, analyze critically the causes, course and prognosis of AA incl. interpretation of their own group of patients. In view of the frequent (and rising) incidence of AA in old age, the authors consider it important to pay attention to this problem also from the aspect of clinical gerontology.

Aged↗
PubMed1989

[Ultrasonography of echinococcosis, toxocariasis and cysticercosis of the liver].

The diagnosis of tissue parasitoses has remained complicated until the present time for variability of clinical picture. Their incidence been increasing due to aimed and accidental findings of foci in parenchymal organs employing new methods of visualization such as computer tomography and especially ultrasonography whose advantage is a good detection rate, availability and a possibility to follow the dynamics of parasitosis development. The authors present a survey of ultra-sonographic findings of the liver in cases of tissue parasitoses occurring in Czechoslovakia, while using their own image documentation. If a focal affection in the liver is established the differential diagnosis considerations should also take into account a tissue parasitosis, whose ultrasound picture may be nonspecific.

Cysticercosis↗
PubMed1989

[Long-term results of surgical treatment of portal hypertension].

Large number of contradictory operative surgeries refer best to embarrasments, existed on this section of surgery. Today, from the amount of operative surgeries prevail the endoscopic sclerotization of the gastroesophageal varices. On basis of retrospective study of 48 portosystemic shunts was showed, that 28 operated patients survive average 8.1 year, till now 4 patients of them are alive, within 8-14 years. In 7 cases of azygoportal deconexion by Torres-Dengi, average time of survive was 2.5 year. There experiences led the authors to elaborate an algorithm of treatment of portal hypertension, where the postosystemic shunts are the portosystemic shunts are the effective palliative operative surgery in indicated cases.

Esophageal and Gastric Varices↗
PubMedDate not supplied

[Epidemiology of anorexia nervosa. Prevalence of anorexia nervosa in female adolescents from the districts of Lisboa and Setubal].

UNLABELLED: Prevalence studies of anorexia nervosa (AN) have shown differences depending of the country and method applied. The partial syndrome is being emphasized. There has been no epidemiological study done on AN in the Portuguese population of continental Portugal. Our objectives were: 1) to study the prevalence of AN in Portuguese populations; 2) to study the presence of partial syndrome and of body image disturbance; 3) to calculate the number of girls dieting; 4) to correlate with other variables. A population of 2,398 girls ranging 10 to 21 years old, from 30 State secondary schools in the Lisbon and Setubal districts were studied. A questionnaire was answered with questions allowing assessment of all DSM IIIR criteria for AN. RESULTS: Prevalence of AN--0.37%, partial syndrome--12.6%, body image disturbance without weight loss--7%, wish to decrease weight in normal or low weight girls--38%, overweight--15.3%, the peak of age for AN was 15 years, the most prevalent socio-economic class for AN was 2 (scale 1 (higher) to 5). School performance was worse with AN and the age menarche was sooner.

Adolescent↗