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Biomedical subjects

M Laurent

Publications and source records attributed to M Laurent.

At least 181 records · Page 10Linked to original sources

Cell-free translation products of basement membrane RNA from the EHS tumor.

The biosynthetic products of the Engelbreth-Holm-Swarm (EHS) tumor and the cell-free translation products of EHS tumor cell RNA were characterized. Six distinct gene products (three laminin polypeptides, entactin/nidogen, and two collagen IV chains) comprising the basement membrane matrix were identified by a combination of proteolytic digestion and immunologic techniques. Analysis of the cell-free translation products using EHS tumor RNA precipitated by anti-laminin serum confirms earlier evidence that there are at least two B chains encoded by different genes. The anti-laminin serum also recognized entactin/nidogen, which was further identified by specific immunoprecipitation with anti-entactin serum. Radiolabeled laminin A chains, synthesized by the EHS tumor in organ culture, were also identified by the anti-laminin serum but were not detected among the cell-free translation products of EHS tumor RNA. Pulse-chase studies of EHS tumor in organ culture as well as in vitro translation of EHS tumor RNA suggest that the precursor forms of alpha 1(IV) and alpha 2(IV) collagen chains are nearly identical in size, with apparent molecular weights of 170,000. The mRNAs encoding these two polypeptides migrate differently on sucrose gradients. It is likely that glycosylation and hydroxylation of collagen IV account for the major differences in molecular weight of mature alpha 1(IV) and alpha 2(IV) chains in the EHS tumor matrix.

Animals↗

Characterization of the 5'-flanking region for the human fibrinogen beta gene.

To identify the possible regulatory sequences in the genetic expression of fibrinogen, a human genomic DNA library raised in lambda EMBL 4 phage was screened using cDNA probes coding for the A alpha, B beta and gamma chains of human fibrinogen. The entire fibrinogen locus was characterized and its organization analysed by means of hybridization and restriction mapping. Among the clones identified, a single recombinant lambda phage contained the beta gene and its 5'- and 3'-flanking regions. A 1.5 kb fragment of the immediate 5'-flanking region was sequenced and S1 mapping experiments revealed three transcription start points. Comparison of this sequence with that previously reported for the same region upstream from the human gamma gene revealed no significant homology which suggests that the potential promoting sequences of these genes are different. In contrast, comparison of the 5'-flanking regions of human and rat beta genes revealed a 142 bp sequence of 80% homology situated 16 bp upstream from the human beta gene. This highly conserved region may well represents a potential candidate for a regulatory sequence of the human beta gene.

Amino Acid Sequence↗

Thrombolysis of acute total occlusion of the left main coronary artery and long-term survival.

A young woman was admitted with acute anterior myocardial infarction. Emergency coronary angiography showed a total occlusion of the LMCA. Selective infusion of streptokinase recanalized the left main coronary artery (LMCA), the circumflex artery, and the first diagonal, but not the entire left anterior descending artery (LAD). The right coronary artery was dominant and normal. The left-sided congestive heart failure was severe; treatment improved the heart failure and the patient was discharged on Day 25. She was readmitted for control 28 months later: she was only moderately disabled and coronary angiography showed the same occlusion of the LAD; result on ejection fraction (right anterior oblique view 30 degrees) was not significant, but circumflex artery recanalization probably preserved lateral wall contraction. The presence of a normal dominant right coronary artery seems to be a very important factor in contributing to initial survival.

Adult↗

Collagen synthesis by long-lived mRNA in embryonic chicken lens.

Lens capsule collagen synthesis by epithelial and fiber cells was examined by immunoprecipitation and collagenase digestion in embryonic and posthatch chicken eye lens. Epithelial cells and lens fibers in the process of terminal differentiation produce alpha 1 and alpha 2 type IV collagen chains. At 6 days of embryonic development in addition to the alpha 1 (IV) and alpha 2 (IV) collagen chains, lens cells produce high molecular weight collagenase-sensitive proteins not immunologically related to type IV collagen. Lens capsule collagen components have been identified in central and outer fibers isolated from 18-day embryos and from 10-day posthatch chicken eyes. At these stages, fibers which have an increasing number of picnotic nuclei still show collagen synthesis due to long-lived mRNA. Analysis of collagen synthesis by lens cells incubated with actinomycin D suggests that stabilization of collagen mRNA occurs in lens fiber cells and to a lesser extent in epithelial cells as early as 6 days of embryonic development.

Age Factors↗

Characterization of genes coding for two major metacyclic surface antigens in Trypanosoma brucei.

In African trypanosomes, only a very small fraction of the total repertoire of variable antigen types (VATs) is expressed by the metacyclic form. In Trypanosoma brucei stock EATRO 1125, the VATs AnTat 1.30 and 1.45 are reproducibly present in about 15% and 4% of the metacyclic population, respectively. The genes encoding the corresponding antigens or variant surface glycoproteins (VSGs) are in telomeres of large chromosomes, as are some non-metacyclic VSG genes from the same stock. Their activation mechanism has been studied in seven independent clones, 3 of which, referred to as 'first wave' metacyclic VATs (M-VATs), have been cloned from the first wave of parasitemia after cyclic transmission. In all these clones, activation of the antigen gene was linked to the transposition of an expression linked copy (ELC) of the gene to a telomeric expression site. For first wave M-VATs, this site seems variable, although restricted to large chromosomes, and it can be re-used for VSG gene expression in the bloodstream form. In 'late bloodstream' M-VATs, isolated from established chronic infections, the active expression site, at the end of a 200 kb chromosome, is the one preferred for the expression of late antigen types. It can be concluded that no characteristic feature in the genomic location and expression mechanism can distinguish metacyclic antigen genes from those expressed in the bloodstream forms, although the control of their expression must clearly be different.

Animals↗

Treatment of bilateral retinoblastoma stage V at the Curie Foundation. 33 cases.

A retrospective study was undertaken on 33 patients with bilateral retinoblastoma in whom one eye at least was classified as stage IV or V (Reese-Ellsworth classification). In most cases the other eye had been enucleated elsewhere. Conservative therapy consisted of primary chemotherapy (vincristine, actinomycin, cyclophosphamide) followed by external beam irradiation, six courses of chemotherapy and, if necessary, by cobalt-60 plaques, xenon arc photocoagulation or secondary enucleation. Ten patients were lost to follow-up, eight patients died or are currently being treated for recurrence, 15 patients are alive and free from disease and 42% of eyes at stage IV or V were saved. These results indicate that primary chemotherapy does not improve the final outcome of stage IV or V retinoblastoma, as compared with primary irradiation.

Combined Modality Therapy↗

Isolation of an alpha 1 type-IV collagen cDNA clone using a synthetic oligodeoxynucleotide.

We have isolated a cDNA clone (pCIV-1-225) for the alpha 1 subunit of basement membrane (type IV) collagen from a cDNA library made from Engelbreth-Holm-Swarm mouse tumor RNA. The cDNA library was screened with synthetic oligodeoxynucleotides derived from published amino acid (aa) sequences (Schuppan et al., 1982). Nucleotide sequence data established the identity of our cDNA clone to encode an alpha 1 type IV collagen. This clone contains 270 aa of the helical region and has three interruptions in the Gly-X-Y repeat unit.

Amino Acid Sequence↗

The use of DNA hybridization and numerical taxonomy in determining relationships between Trypanosoma brucei stocks and subspecies.

The nuclear DNAs of 71 trypanosome stocks from different African countries, representative of the three Trypanosoma brucei subspecies, and one T. evansi stock, have been analysed by the combined use of restriction endonuclease digestion, gel electrophoresis and molecular hybridization with both trypanosome surface-antigen-specific and undefined genomic DNA probes. In contrast with T. brucei brucei and T. brucei rhodesiense stocks, all the T. b. gambiense stocks are characterized by a conserved, specific DNA band pattern, regardless of the probe. This allows T. b. gambiense to be non-ambiguously identified. On the contrary, T.b. brucei and T. b. rhodesiense, which could not be discriminated by the same criteria, both yield highly variable DNA band patterns. Our data confirm that domestic animals like pig, dog and sheep constitute a potential reservoir for T.b. gambiense. Using a numerical analysis of the DNA hybridization patterns we have measured the degree of similarity between the 72 trypanosome stocks. This investigation shows that all T.b. gambiense stocks are included in the same homogeneous population, while the stocks from the two other subspecies seem to be distributed in several heterogeneous groups, some of these showing correlation with the geographical origin of the trypanosomes. It is concluded that (i) T.b. gambiense stands out as a real subspecies that has undergone a distinct evolution relative to the 'non-gambiense' group, (ii) the alleged T.b. rhodesiense subspecies does not fit with any of the groups evidenced by our cladistic analysis and hence does not appear as a distinct subspecies and (iii) 'non-gambiense' trypanosomes are probably evolving much more rapidly than T.b. gambiense. Different aspects of trypanosome relationships and evolution are discussed.

Africa↗

Thermoinactivation of human IgE: antigenic and functional modifications.

The thermoinactivation kinetics of IgE were studied in experimental models revealing the antigenic properties and the basophil-sensitizing capacity of these immunoglobulins. A pool of human sera containing anti-Dactylis glomerata (Dg) IgE was heated from 5 min up to 4 hr at 56 degrees. The IgE antigenicity was tested by two polyclonal 125I-labelled anti-IgE antibodies; one anti-IgE was specific of the whole Fc epsilon region, while the other had a specificity restricted to the D epsilon 2 domain. Radioimmunoassays showed that the D epsilon 2 epitopes were more rapidly altered than the D epsilon 1 epitopes. The capacity of IgE to bind to basophil Fc epsilon receptors was assayed by passive sensitization experiments. Basophil sensitivity towards the Dg pollen extract was tested by histamine release experiments in the presence of this allergen. A progressive decrease in cell sensitivity was observed when IgE samples used for cell sensitization were heated for longer than 5 min. Thermoinactivation kinetics of IgE revealed an unexpected increase in the apparent quantity and biological activity of IgE heated for 5 min at 56 degrees. This fact could be due to auto-anti-IgE antibodies linked to the unheated IgE and which interfere with the biological activities of IgE and their quantification.

Basophils↗

[Evaluation of aortocoronary bypass using exercise myocardial thallium 201 scintigraphy].

The surveillance of aortocoronary bypass grafts is a difficult problem. Clinical examination and exercise testing are unable to give a complete evaluation of the operative results and cardiac catheterisation with radiological opacification of the grafts are not without risk and cannot be repeated periodically. Therefore, radioisotopic methods have been proposed as a means of assessing aortocoronary bypass grafts. The aim of this study was to evaluate postoperative myocardial perfusion by Thallium 201 scintigraphy. The authors compared pre and postoperative scintigraphies in 37 patients undergoing aortocoronary bypass surgery (36 men and 1 woman, average age: 53.9 years). Preoperative coronary angiography showed 9 cases of single vessel disease, 11 cases of double vessel diseases and 17 cases of triple vessel disease. Seventy one bypass grafts were performed (average 1.92 grafts/patient): 37 on the LAD, 15 on the circumflex, 10 on the diagonal and 9 on the right coronary. All patients were submitted to the same protocol before surgery and during the third postoperative month; Clinical examination, ECG, exercise stress testing and Thallium 201 myocardial scintigraphy. The results confirm the improvement in myocardial perfusion after coronary bypass surgery. The percentage of pathological scintigraphic segments fell from 42 per cent before surgery to 27 per cent after surgery (p less than 0.01). The total Thallium perfusion index improved significantly after surgery from 9.3 +/- 2 to 7.7 +/- 1.9 (p less than 0.01). Thallium 201 scintigraphy was superior to clinical examination and exercise testing in the assessment of graft patency, identifying 2 postoperative infarctions inapparent on clinical examination, excluding postoperative non-anginal chest pain and evaluating myocardial perfusion in patients who had sub maximal postoperative exercise stress tests. The relatively non traumatic character of Thallium 201 scintigraphy makes it the best non-invasive method of assessing aortocoronary bypass graft patency.

Adult↗

[Neuropathological study of 12 centenarians: the incidence of Alzheimer type senile dementia is not particularly increased in this group of very old patients].

The brains of 12 patients aged more than 100 years were studied neuropathologically. These were all women who had been long-stay patients at the Charles Foix Hospital, Ivry. On the basis of a retrospective examination of the clinical records the patients were classified as demented or non-demented. No attempt was made to evaluate their mental status more precisely because of the prevalence of deafness (in 10) and blindness (in 7) and also because of the difficulty in assessing mild cognitive changes in institutionalized patients. Three patients were considered to have been demented according to the criteria of the DSM3 (1980). In the brain of one demented case the pathology was that of Alzheimer's disease, in one there were multiple infarcts and in the third there were both senile and vascular changes. The findings in this study are in accordance with the reports of others and indicate that the incidence of senile dementia of the Alzheimer type is not increased in people of very advanced age. Neuropathological findings included reduced brain weight; neurofibrillary tangles in hippocampal neurons of every case as well as in neocortical neurons (absent from neurons of the substantia innominata in only 1 case); senile (neuritic) plaques were found commonly in the hippocampus, less so in neocortical areas (senile plaques totally absent in only one case); granulovacuolar degeneration in hippocampal neurons in every case; amyloid angiopathy present in 9 and mineralization of vessels in 10 cases; hyaline change in vessel walls and abundant lipofuscin in neurons and astrocytes were constant findings. No Lewy bodies were seen.

Aged↗

[Auricular fibrillation in the elderly. Indicators of risk and cerebral prognosis].

Cardiovascular anomalies contributing to development of atrial fibrillation (AF) and subsequent cerebral repercussion have been studied by analysis of clinical, electrocardiographic and anatomicopathological data for 131 elderly (85.16 +/- 6.7 years) medium- and long-term hospital patients. AF was seen in 22.14% of cases and seems more frequent in the ninth decade than in the eight. Predisposing factors were coronary alterations of repolarization (p less than 0.001), myocardial hypertrophy (less than 0.01), hypertension with cardiac repercussions (p less than 0.01), intraventricular conduction disorders, left anterior hemiblock excepted (p less than 0.05) and mitral valvulopathy. AF developed in 12% of cases without apparent cardiopathy. The risk of cerebral infarct was marginally greater in the presence of AF than in its absence; the risk was clear for paroxysmal forms and nil when AF developed in a healthy heart. In contrast, intellectual deterioration and cerebral hypotrophy were significantly more marked (p less than 0.01) in patients presenting AF. This affirmation is evidence for long-term hemodynamic repercussions of arrhythmia affecting cerebral blood flow and constitutes an argument for re-establishment of sinusal rhythm.

Aged↗

Selective decrease of type I collagen synthesis in Fraser mice skin.

Quantification and biosynthesis of type I and type III collagens were determined in skin of control and Fraser mice (CatFraser mutation), which exhibit a genetically determined cataract. Skin organ cultures were labelled with [3H]proline. Pepsin-solubilized collagens were studied using three different approaches: (a) differential salt precipitation at neutral pH, followed by SDS-polyacrylamide gel electrophoresis; (b) differential salt precipitation at acid pH followed by SDS-polyacrylamide gel electrophoresis. (c) CNBr peptide analysis. These methods gave consistent and reproducible results, indicating a selective decrease of type I collagen in Fraser mouse skin as compared to control mouse skin. Metabolic labelling of skin organ cultures showed a decreased specific radioactivity of hydroxy[3H]proline in type I collagen of Fraser mouse skin. The concordant results of these experiments suggest a genetically determined alteration of interstitial collagen metabolism in the Fraser mutation apparently specifically concerning the expression of type I collagen gene(s).

Animals↗