PubMed Health⌕ Search

Biomedical subjects

A Lagarde

Publications and source records attributed to A Lagarde.

At least 19 recordsLinked to original sources

Diagnostic sensitivity of three tumour markers in non-small cell lung cancer: a pilot study.

BACKGROUND: Three tumour markers (CEA, CYFRA 21.1 and CA125) were evaluated for diagnostic sensitivity in newly diagnosed, untreated non-small cell lung cancer. METHODS: In the 24 patients studied, the tumours were classified histologically as 15 squamous cell carcinomas and 9 adenocarcinomas. In 19 cases, the disease was confined to the lung (M0); 5 cases presented with metastatic disease at the time of diagnosis (M1). RESULTS: CA125 displayed the best overall sensitivity (62%) and also when only localised disease was evaluated (63%). CA125 was the most sensitive marker for adenocarcinomas (89%), with values differing significantly with histological type (p < 0.005). CYFRA 21.1 was most sensitive in squamous cell carcinomas (53%); this was the only marker which was elevated in all cases involving metastatic disease, and exhibited a significant correlation with stage (p<0.02). CEA presented the poorest overall sensitivity (42%). The overall sensitivity of the three-tumour marker association was 79% and the best combination of two markers was CYFRA 21.1 + CA125 (75%). CONCLUSIONS: This pilot study allows recommendation of the associated use of these two markers as first choice of diagnostic aid in non-small cell lung cancer. Further measurements, including specificity studies in benign lung diseases, should be performed to confirm these results.

Journal Article↗

Insulin-like growth factor binding protein 1 level in amniotic fluid: correlation with birth weight.

Insulin-like growth factor binding protein 1 is the predominant insulin-like growth factor binding protein in amniotic fluid. It is produced by the decidua and by fetal tissues, and it is thought to play an important role in fetal growth. We have measured this protein in 58 samples of amniotic fluid, from 13 to 19 gestational weeks, and found a highly significant negative correlation with fetal weight at birth. We conclude that the level of insulin-like growth factor binding protein 1 in amniotic fluid at midpregnancy is a good marker of fetal growth failure.

Amniotic Fluid↗

[Use of a medium and long chain triglyceride mixture for parenteral nutrition in a university hospital: results of an internal audit].

OBJECTIVES: The aim of this study was to determine whether a medium and long chain triglyceride mixture for parenteral nutrition is used in accordance with indications and contraindications in hospital practice. METHODS: Patient data recorded in 30 consecutive patients included illness, nutritional status, laboratory findings before nutrition as well as indications and contraindications for parenteral nutrition. RESULTS: When expressed in g.kg-1.day-1 maximal recommended doses of the mixture were exceeded in 32% but there was no excess when expressed in g.kg-1.hr-1. Serious hepatic insufficiency was present in 11% of the patients, 38% had hypertriglyceridemia and one had serious coagulopathy. There were 3 contraindications for the mixture. CONCLUSION: Indications for using this emulsion were respected, but there were contraindications in 45% of the cases. These contraindications are however questionable as is the daily dosage. Because the mixture seems better for use in many cases of parenteral nutrition, it would appear best to discuss the prescription case by case.

Adult↗

Genetics of hereditary colon cancer: a model for prevention.

Accompanying the explosion of genetic information about cancer is the technology to allow a better understanding of carcinogenesis and tools that can be exploited in the diagnosis and management of cancers. The familial forms of colorectal cancer, including familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer offer the most tangible examples of potential improvements in mortality and morbidity incorporating molecular markers. This article reviews the current direct applications of molecular genetics in identifying the risk, prevention and management of colon cancer. The limitations and current controversies in the field are discussed, including research strategies being adopted to solve the remaining problems. Parallel strategies in familial breast cancer and ovarian cancer are being developed to bring the medical profession into the molecular age of cancer management.

Adenomatous Polyposis Coli↗

Twenty-nine day study of stability for six different parenteral nutrition mixtures.

: BACKGROUND: The aim of the study was to assess the particle size stability of six parenteral nutrition regimens, fitted to various pathologies, and used by the University Hospital of Limoges. The mixtures contained glucose (30 or 50%), amino acids (Hyperamine(R)25), and either long-chain triglycerides (20% Intralipide(R)) or a combination of medium and long-chain triglycerides (20% Médialipide(R)). The regimens were not supplemented. RESULTS: The visual examinations, particle size analysis and physico-chemical tests, carried out during a long storage period, did not reveal any significant evolution of the lipid emulsions. All the tested formulae were stable for 28 days at 4 degrees C plus 24 h at room temperature. CONCLUSIONS: It was concluded that the choice of lipid emulsions depends, for these formulae, on the metabolic and clinical needs of the treated patients.

Journal Article↗

[Anomalies of enamel formation in subjects with maxillary clefts].

A structural and ultrastructural study of teeth located in the vicinity of maxillary cleft and teeth located outside the cleft region, was made in 12 cases, using correlated light microscopy, microradiography and SEM. All teeth directly involved in cleft process presented gross hypoplasia of the crown where the enamel surface was hypomineralized. Globular calcified masses of different radiodensity were seen on the hypomineralized enamel surface. The teeth located outside the cleft region presented less pronounced anomalies constituted by isolated or group microhypoplasia on hypomineralized enamel. The observation of enamel pearl was not pathognomonic of maxillary cleft.

Cleft Lip↗

Structural and ultrastructural study of the teeth in a suspected case of pseudohypoparathyroidism.

Two premolars removed from a 14 year old girl, with suspicion of pseudohypoparathyroidism (PHP) have been studied, using several of the correlated techniques applied to the study of calcified tissues (light microscopy, microradiography and scanning electron microscopy). Enamel gross and micro hypoplasia, hypomineralization of the enamel surface and dentin hypocalcification were similar to dental abnormalities observed in pseudohypoparathyroidism. Microradiography showed for the first time calcifications present in blood vessels of the dental pulp. Light microscopy and SEM revealed dystrophic globular calcifications within enamel hypoplastic pits. Cemental changes consisting of hypoplasia, aplasia, localized hyperplasia and cementicules were described for the first time. It is suggested that enamel, dentine and pulp abnormalities observed in the present case might be pathognomonic of PHP.

Adolescent↗

Genetic evidence for progressive selection and overgrowth of primary tumors by metastatic cell subpopulations.

We have exploited random insertions of transfected DNA as unique clonotypic markers to follow cell lineages during primary and metastatic tumor growth of a mouse mammary adenocarcinoma, SP1. Southern analysis was undertaken of primary solid tumors and metastases obtained after injection of a pooled population of individual SP1 transfectants, or reconstituted mixtures of genetically marked metastatic and unmarked nonmetastatic cells. Here we provide evidence for the reproducible selection and eventual overgrowth of primary tumors by genotypically distinct metastatic clones, thereby illustrating that late-state, advanced primary tumors can evolve to become biologically similar, or even identical, to distant metastases. The selective growth advantage of metastatic cells within primary tumors was shown to occur despite the fact that tumors generated by both metastatic and nonmetastatic SP1 cell populations grew at comparable growth rates when injected and analyzed separately. The extent of the local growth advantage manifested by individual metastatic clones varied considerably, from 5- to 50-fold. Clonal overgrowth was also observed whether the tumor cells were injected ectopically, or orthotopically (i.e., into the mammary fat). This type of experimental approach should provide new insights into the dynamics of tumor progression and metastasis, the lineage relationship of primary tumors to metastases, the influence of clonal interactions on tumor behavior, and the physiological changes which are causative of malignant disease.

Adenocarcinoma↗

Deregulation of hamster fibroblast proliferation by mutated ras oncogenes is not mediated by constitutive activation of phosphoinositide-specific phospholipase C.

Stable expression of high levels of activated forms of Haras (T24) or v-Ki-ras by transfection of Chinese hamster lung fibroblasts (CCL39) yielded cells highly tumorigenic in nude mice. Two classes of transformed cells were distinguished, one with moderate p21 expression (10-fold increased) had retained growth factor dependency, the second with higher level of p21 (greater than 50-fold) appeared autonomous for growth. Neither class of transformants expressing Ki-ras or Ha-ras displayed a significant basal activity of polyphosphoinositide-specific phospholipase C, measured either in serum-starved cells or during exponential growth in the presence of growth factors of the tyrosine kinase family (EGF, FGF, insulin). In the growth-factor-dependent class of T24-Ha-ras-transfected cells (clone 39THaB), phospholipase C could be stimulated normally by serum, thrombin and AlF-4. In the more growth autonomous class (clones 39THaC and 39Ki9), release of inositol phosphates after stimulation with thrombin or serum was drastically reduced. This desensitization, apparently at the receptor level since the response to AlF-4 persisted, is, however, not specific to ras expression. We observed it to the same degree in polyoma virus-transformed CCL39 cells. Finally, expression of mutated forms of p21 ras did not abrogate the sensitivity of phospholipase C activation to pertussis toxin. We conclude that the transforming potential of activated forms of p21ras does not result from persistent activation of phospholipase C and that ras GTP-binding proteins cannot substitute for Gp.

Animals↗

Clonal dominance of primary tumours by metastatic cells: genetic analysis and biological implications.

A new method is described for analysing the clonal evolutionary dynamics of tumour growth and the lineage relationship of primary tumours to their metastases. It exploits random integrations of transfected plasmid or retroviral infected (proviral) DNA as a means of generating very large numbers of uniquely marked cell clones in a single-step selection whose fates can then be tracked during progressive tumour growth. Using a mouse breast adenocarcinoma we undertook experiments in which syngeneic mice were injected with a mixture of very large numbers of uniquely marked cell clones, only one or a few of which were metastatic, or with reconstituted mixtures containing a genetically tagged metastatic clone with an excess of non-marked non-metastatic tumour cells. Among the results we summarize is the finding that spontaneous metastases developed in a non-random fashion from genotypically distinct cell clones. They were clonal or biclonal at the time of analysis. We also found that the progeny of a single metastatic clone could eventually overgrow the primary tumour. Thus malignant (metastatic) cells may manifest a striking growth advantage within the primary tumour site as well as for dissemination and growth at distant, secondary sites. As a result, late-stage advanced primary tumours, if left intact, may evolve to become biologically similar or equivalent to distant metastases. This 'clonal dominance' phenomenon can reconcile many of the discrepant experimental findings with respect to the putative selective nature of metastatic phenotype. Furthermore, it has important consequences for understanding one source of biological variability in experiments in which different primary tumours are compared to each other or to metastases; it also has implications for theories regarding the clonal origin of neoplasms, and for the physiological and biochemical changes that cause malignant disease.

Animals↗

v-fps protein-tyrosine kinase coordinately enhances the malignancy and growth factor responsiveness of pre-neoplastic lung fibroblasts.

The v-fps oncoprotein was expressed in a pre-neoplastic, growth factor-dependent Chinese hamster lung fibroblast line (CCL39) to study its effect on growth controls and on the induction of malignancy. Two transfectants were characterized which expressed low (39FPS-8) or high (51FPS-6) levels of P130gag-f ps protein-tyrosine kinase activity. 39FPS-8 cells still arrested in quiescence when deprived of growth factors, but developed an increased sensitivity to the mitogenic actions of epidermal growth factor (20-fold) and alpha-thrombin (50-fold), although not to insulin. In contrast, 51FPS-6 cells completely escaped growth controls, divided in serum-free medium, and were insensitive to further growth factor stimulation. Both transfectants produced rapidly growing tumors in nude mice that formed pulmonary metastases from a subcutaneous site, unlike the parental cells which are non-metastatic. 51FPS-6 cells were comparatively more efficient than 39FPS-8 cells in colonizing the lungs after intravenous inoculation. The v-fps tyrosine kinase therefore induces a partial to complete relaxation of growth factor-mediated controls on the CCL39 cell cycle, with the extent of factor independence reflecting the amount of P130gag-f ps synthesized. This reduction in growth factor requirements correlates with the capacity of v-fps to confer the attributes of metastatic tumors upon preneoplastic CCL39 fibroblasts. We speculate that increased sensitivity to growth factor stimulation represents a common mechanism by which tumor cells acquire metastatic properties.

Animals↗

[Structure, ultrastructure and microanalysis of the enamel of teeth near maxillary clefts].

Teeth located in the vicinity of cleft palate were studied using correlated light microscopy, microradiography, SEM, TEM and microanalysis. Structural, ultrastructural and chemical abnormalities were found in enamel. The enamel surface presented micro and gross hypoplasia, associated with hypomineralization. Microradiography showed the antenatal enamel to be more mineralized than postnatal enamel. Microanalysis showed the Ca/P ratio measured at the enamel surface to be higher in the teeth associated with cleft palate, compared with controls. The Ca/P value was due to a Ca increase and a P decrease in the enamel surface. The Ca increase was correlated with a decrease in Mg, supporting the hypothesis of a Mg/Ca substitution in the apatitic structure.

Adolescent↗

[Murine cloned cells related to basophil-mast cell granulocytes, spontaneously cytotoxic toward tumor cells].

Two independent cloned cell lines were derived following the in vitro expansion of spleen and bone-marrow cells suspensions from DBA/2 Mice in the presence of a conditioned medium containing interleukin II. They exhibit a spontaneous cytotoxicity towards two tumors of leukemic origin. The presence of cytoplasmic granules, their staining properties, the typing of surface markers and enzyme activities suggest that they belong to the basophil-mast cell lineage.

Animals↗

Evidence for an electrogenic 3-deoxy-2-oxo-D-gluconate--proton co-transport driven by the protonmotive force in Escherichia coli K12.

Evidence is presented indicating that the carrier-mediated uptake of 3-deoxy-2-oxo-D-gluconate and D-glucuronate in Escherichia coli K12 is driven by the deltapH and deltapsi components of the protonmotive force. 1. Approximately two protons enter the cells with each sugar molecule, independent of the sugar and the strain used. 2. In respiring cells, the magnitude of the pH gradient alone, as measured by distribution of [3H]acetate, appears to be insufficient to account for the chemical gradient of 3-deoxy-2-oxo-D-gluconate that is developed between pH 6.0 and 8.0. 3. If the external pH is varied between 5.5 and 8.0, 3-deoxy-2-oxo-D-gluconate uptake is gradually inhibited by valinomycin plus K+ ions, whereas the inhibition caused by nigericin is concomitantly relieved, thus reflecting the relative contribution of deltapH and deltapsi to the total protonmotive force at each external pH. 4. 3-Deoxy-2-oxo-D-gluconate can be transiently accumulated into isolated membrane vesicles in response to an artificially induced pH gradient. The process is stimulated when the membrane potential is collapsed by valinomycin in the presence of K+ ions.

Biological Transport, Active↗