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L David

Publications and source records attributed to L David.

At least 73 records · Page 4Linked to original sources

Loss of a novel mucin-like epithelial glycoprotein in oral and cervical squamous cell carcinomas.

Stratified squamous epithelia of oral and cervical mucosa express high levels of simple mucin-type O-linked carbohydrates, and these are known to undergo structural changes in relation to epithelial differentiation and neoplastic transformation. O-glycans in these epithelia are associated with the cell membrane, but the identity of the carrier molecule(s) remains largely unknown. We report here the identification of a membrane-bound M(r) 200,000-250,000 glycoprotein (gp230) that is expressed in stratified squamous epithelia of the oral cavity. Western blot analysis identified gp230 as a major carrier of simple-mucin type carbohydrate antigens in buccal nonkeratinized mucosal epithelium, suggesting that it may represent a mucin-like molecule. A monoclonal antibody PANH4 defining a protein epitope of gp230 was generated. The PANH4 epitope was localized by immunohistology to suprabasal cell layers of buccal epithelium and was also found in larynx, esophagus, vagina, and exocervix, but not in epidermis. Data showed that gp230 was distinct from MUC1 or CD44. It is interesting that in most cases gp230 was not expressed in squamous cell carcinomas of buccal and cervical mucosa. A few moderately differentiated carcinomas, mainly from cervix, expressed the gp230 epitope. The results suggest that a membrane-bound mucin-like molecule, gp230, is associated with the differentiated phenotype of normal mucosal stratified squamous epithelia and that expression of gp230 generally is lost in severe oral epithelial dysplasia and squamous cell carcinomas of oral and cervical mucosa.

Adult↗

Screening for neuroblastoma in France: methodological aspects and preliminary observations.

A pilot study of neuroblastoma mass screening was initiated in January 1990 in the Rhône French district. The expected number of births per year is 26,000. The study is designed for a 5-year period with three major goals: 1) measurement of the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the technical value of high-pressure liquid chromatography (HPLC) as a screening method; and 3) detailed biological characterization of all detected tumors. 61,551 children were screened between May 1, 1990 and December 31, 1993. Participation was 69% in 1990, 81.5% in 1991, and over 83% in 1992. HPLC was a satisfactory assay method. The number of clinical examinations required for positive tests as defined in the protocol is 1 per 3,621 tests. The false positive rate is 1 per 3,583 tests. Eight neuroblastomas were discovered by-screening (one stage I, three stage II, one stage III, three stage IVs). All are alive and well but were good prognosis cases according to the main prognostic factors. Five patients were discovered before screening (so called Halo effect): one stage I, one stage III, three stage IVs. One died of disease and four are alive in complete remission after treatment. Two patients were false negative (one stage III with N-myc amplification, one stage IV with bad prognosis features) and three cases of neuroblastoma were missed because of noncompliance with the screening program. This pilot study concludes on the feasibility of a mass screening program in France. The estimated cumulative incidence of neuroblastoma at 3 years is 1 per 4,375 living births and overdiagnosis is probable. All the detected cases were of good prognosis and the false negative ones were poor prognosis cases.

Child, Preschool↗

Ki67 labelling index in gastric carcinomas. An immunohistochemical study using double staining for the evaluation of the proliferative activity of diffuse-type carcinomas.

The aim of the present study was to clarify the conflicting recorded data on the proliferative features of gastric carcinoma. The Ki67 labelling index (Ki67 LI) was evaluated using MIB-1 in 43 carcinomas (24 diffuse and 19 intestinal). In 18 cases, differential counts were performed in superficial and deep layers. In ten diffuse carcinomas with a prominent desmoplastic response, Ki67 LI was evaluated in sections double-stained with MIB-1 and CAM5.2. Flow cytometry was performed in 26 cases. Ki67 LI of diffuse carcinomas (36.3 +/- 19.0) was not significantly different from that of intestinal carcinomas (28.2 +/- 18.5). Ki67 LI was significantly higher (P = 0.006) in superficial than in deep areas (41.9 +/- 22.7 and 29.7 +/- 19.7, respectively) regardless of histological tumour type. No significant relationship was observed between Ki67 LI and wall invasion, lymph node metastasis, vascular invasion or ploidy. The following conclusions were drawn: double immunostaining techniques are apparently the best way to overcome the underestimation of cell proliferation in diffuse gastric carcinomas with a prominent desmoplastic response; the diffuse and intestinal types of gastric carcinoma have proliferation rates within the same range, even when the comparison is restricted to diploid tumours; and, finally, the major pool of proliferating cells resides in the superficial areas of gastric carcinomas, regardless of the histotype, which should be taken into consideration when overall counts are performed, using either immunohistochemical markers in tissue sections or suspensions of nuclei in flow cytometry.

Adenocarcinoma↗

Tetra- and pentanucleotide short tandem repeat instability in gastric cancer.

The association between genetic instability in repetitive DNA domains and cancer has been reported in different types of malignancies. In this work we perform a comparative study of 29 gastric tumors with paired normal tissue using seven tetra-(FES/FPS, VWA31/A, HTPO, TH01, MBPB) and pentanucleotide (CD4, TP53) STR polymorphic markers regarding loss of heterozygosity and replication error status. Furthermore, we compare the gene frequencies obtained in normal tissue from patients with those of a normal control population from the same area, looking for allele associations between any of these polymorphic loci and gastric cancer risk. The results have shown that FES/FPS and TP53 present the higher rates of somatic instability. The observed results for TP53 are in accordance with those previously reported in gastric carcinogenesis, while instability of FES/FPS is for the first time reported in this tumor type. Our data suggest that different loci show different rates of instability and/or loss of heterozygosity and do not seem to consist of a result of an RER+ phenotype affecting several genomic repetitive domains. Furthermore, the instability in markers TH01, MBPB, TP53, and FES was generally detected in genotypes involving alleles with a high number of repeats. Comparing gene frequencies in patients and normal controls, no significant differences were found, although longer alleles are consistently more frequent in patients for the markers MBPB, TH01, and CD4.

Alleles↗

[Vae soli!].

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France↗

MUC1 gene polymorphism and gastric cancer--an epidemiological study.

Gastric carcinoma is a major cause of cancer death worldwide and, like most human cancers, probably develops after environmental insults acting on normal individuals and/or individuals with increased genetic susceptibility. Mucins are attractive molecules to study the relationship between genetics and environment because they play an important role in the protection of gastric mucosa against environmental insults and exhibit a highly polymorphic genetic variation. We performed a case-control study using Southern blot analysis to evaluate the MUC1 gene polymorphism in a series of blood donors (n = 324) and in patients with gastric carcinoma (n = 159). We found that the distribution of MUC1 alleles is significantly different in the two populations and that small MUC1 alleles and small MUC1 genotypes are significantly more frequent in patients with gastric carcinoma than in controls. Individuals with small MUC1 genotypes are at increased risk for gastric carcinoma development.

ABO Blood-Group System↗

Fast healing after laser skin resurfacing. The minimal mechanical trauma technique.

BACKGROUND: Laser resurfacing is rapidly becoming a widely used method of skin ablation for cosmetic improvement. The technique with which the instrument is used can make the difference between obtaining the desired result with a benign postoperative period and one with unnecessary complications. OBJECTIVE: This paper describes a technique that maximizes the benefits while minimizes the risks in using this highly advanced instrument. METHODS: We have limited the areas where multiple passes are done to areas that have rhytides; for the rest of the skin a single pass is done and the final carbonized eschar is not removed. RESULTS: Faster healing and less complications. Shorter operative and anesthesia times. Greater patient acceptance and satisfactory cosmetic results. CONCLUSIONS: This technique provides a safer, faster, and satisfactory cosmetic results with a much smaller possibility of the complications seen with conventional methods.

Anesthesia, Intravenous↗

Utility of helical computed tomography in the study of arytenoid dislocation and arytenoid subluxation.

Conventional computed tomography (CT) has been considered a mainstay in the evaluation of the larynx. A major difficulty with utilizing this modality, especially in the study of the arytenoid, is the time necessary to perform a thin-slice examination through a structure that has a propensity to move with respiration and swallowing. Helical CT not only significantly reduces the time necessary to study the larynx, but enables one to perform multiple high-resolution multiplanar reconstructions. Eleven patients with arytenoid abnormalities documented by strobovideolaryngoscopy or direct laryngoscopy were imaged with helical CT. A comprehensive radiographic examination illustrating the cricoarytenoid relationship in all of the subjects was completed in less than 20 seconds by using axial reconstructions in 2-mm-thick slices at 1-mm intervals, with subsequently derived sagittal and coronal reconstructions. Helical CT may be a useful adjunct in the diagnosis of arytenoid subluxation or dislocation.

Adult↗

MUC6 gene polymorphism in healthy individuals and in gastric cancer patients from northern Portugal.

Mucins exhibit a high degree of genetic polymorphism because of the presence of a variable number of tandem repeats. The aims of this work were to describe the MUC6 gene polymorphism in the Portuguese population and to evaluate whether MUC6 gene polymorphism was involved in individual susceptibility to gastric cancer development, as observed previously for the MUC1 gene. We found that the 10 alleles identified in the population of blood donors (n = 376), by Southern blot analysis, were also found in gastric cancer patients (n = 157). However, significant differences in allelic frequencies between the two populations were observed for 4 of the 10 alleles, in agreement with those described previously for the MUC1 gene; the largest allele was more frequent in blood donors, and smaller alleles were more frequent in gastric cancer patients. Our results suggest that MUC6 gene polymorphism is involved in the predisposition to gastric carcinoma development.

Adult↗

A 5-year (1990-1994) neuroblastoma screening feasibility study in France. Methodology and preliminary observations.

INTRODUCTION: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990-1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26,000 births per year). METHODS: Vanillylmandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT. VMA and HVA were expressed as microgram/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. RESULTS AND DISCUSSION: The overall participation rate for the 5-year period was 82.2%. Out of 105,293 infants tested from 128,126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty-five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastomas as it is presently being followed up.

Chromatography, High Pressure Liquid↗

Identification of residues of Rhodobacter capsulatus ferredoxin I important for its interaction with nitrogenase.

In Rhodobacter capsulatus, ferredoxin I (FdI) serves as natural electron donor to nitrogenase. In order to probe amino acid residues possibly involved in the interaction with dinitrogenase reductase, FdI was subjected to site-specific mutagenesis. A three-dimensional structure of FdI was designed by computer modelling and used for selecting target residues. Mutant ferredoxins bearing substitutions of surface residues, as well as a variant having a Met2 --> Tyr replacement in the vicinity of one cluster, have been constructed. All FdI variants were expressed to similar levels both in Escherichia coli and in a FdI-deleted mutant of the natural host. Once purified, the mutant ferredoxins exhibited molecular and spectroscopic properties almost identical to wild-type FdI. Determination of the reduction potential of FdI by cyclic voltammetry gave an E'o of -510 mV (pH 7.6) for both clusters, which is one of the lowest values reported for a 2[4Fe-4S] ferredoxin. Only the [Tyr2]FdI variant showed a significant difference in redox potential (delta E'o = -15 mV). Based on in vitro assays, a [Glu27, Glu28]FdI double mutant exhibited a twofold decrease in the electron transfer rate to dinitrogenase reductase while the affinity of this mutant for the enzyme was barely affected. On the other hand, an Asp36 --> His substitution resulted in a sevenfold increase of the apparent Km for dinitrogenase reductase. Unlike FdI and the other mutant ferredoxins, the [His36]FdI variant also failed to form a cross-linked complex with dinitrogenase reductase upon incubation with a carbodiimide. It is concluded that Asp36 in FdI probably participates in the interaction between the two protein partners. Nevertheless, all the FdI mutants proved competent in restoring a wild-type phenotype when expressed in a FdI-deleted mutant background, indicating that none of the studied residues was absolutely critical for electron transfer to nitrogenase.

Amino Acid Sequence↗

Establishment and characterization of two cell lines derived from human diffuse gastric carcinomas xenografted in nude mice.

Two human diffuse gastric carcinoma cell lines were established in vitro from xenografted tumours serially passaged in nude mice. Of 12 primary diffuse gastric carcinomas, 7 were successfully xenografted in nude mice (58.3%). Short-term primary cultures were achieved in all the xenografted lines. However, only 2 of the 7 short-term primary cultures were established as long-term cultures (GP202 and GP220). GP202 cells are larger than GP220 cells, show less abundant intercellular junctions at the ultrastructural level and grow in culture as a compact thin monolayer. The GP220 cells grow preferentially in small clusters attached to the monolayer, with a subpopulation of floating cells. Both lines have cells containing small mucin vacuoles in the cytoplasm and cells displaying a typical signet-ring shape. GP202 cells grow as solid tumours in nude mice but GP220 cells do not give rise to tumours. The flow cytometry and karyotype analysis showed aneuploidy in GP202 cells, with many numerical and structural chromosomal abnormalities, and diploidy in GP220 cells, with several structural chromosomal abnormalities. The CDw75 and Tn antigens are more prominently expressed in GP202 cells than in GP220 cells. T antigen is only expressed in GP202 cells, whereas only GP220 cells express EGFR. Sialosyl-Tn is not expressed in either of the cell lines. The gastric cancer cell lines described in this paper represent a valuable addition to the small number of diffuse gastric cancer cell lines currently available and also provide a good model for further in vitro and in vivo studies of gastric carcinogenesis.

Adenocarcinoma↗

Late MR follow-up of hypothalamic hamartomas.

The absence of changes over time in the diagnostic features of suspected hypothalamic hamartomas is of paramount importance. Since magnetic resonance (MR) imaging is very sensitive to modifications in the brain parenchyma, a late MR follow-up study was performed in five children. In all cases, the diagnosis of hypothalamic hamartoma has been suspected on the basis of the association of central precocious puberty and the presence of a mass in the inferior aspect of the hypothalamus, demonstrated on previous MR studies. Late MR evaluation (after a mean of 39 months) demonstrated stability of the lesions in shape, size, and signal intensity. In three cases the lesions demonstrated a rim of isointense signal with a hyperintense center on T2-weighted sequences. In two cases a Chiari I malformation was found in association with the hypothalamic malformation. In one case a pineal cyst was demonstrated. These unusual findings are discussed. Late MR follow-up showed the absence of changes in the lesions over time, allowing the diagnosis to be confirmed.

Arnold-Chiari Malformation↗