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Biomedical subjects

L David

Publications and source records attributed to L David.

At least 109 records · Page 6Linked to original sources
PubMed1993

Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome.

Microsatellite instability implying multiple replication errors (RER+ phenotype) characterizes a proportion of colorectal carcinomas, particularly those from patients with the hereditary non-polyposis colorectal carcinoma syndrome. We studied the incidence of microsatellite instability in more than 500 sporadic tumors representing 6 different types of cancer. Apart from colorectal carcinoma [see the paper by Lothe et al. (Cancer Res., 53:5849-5852, 1993)] the RER+ phenotype was found in 18% (6 of 33) of gastric carcinomas and 22% (4 of 18) of endometrial carcinomas. In contrast, no evidence of this abnormality was detected in cancers of the lung (N = 85), breast (N = 84), and testis (N = 86). Importantly, the first three cancers, as opposed to the latter three, are characteristic of the hereditary non-polyposis colorectal carcinoma syndrome. These findings suggest that the cancers belonging to the hereditary non-polyposis colorectal carcinoma tumor spectrum may have essential pathogenetic steps in common, including a tendency to multiple replication errors.

Chromosome Deletion↗
PubMed1993

Biosynthetic basis of incompatible histo-blood group A antigen expression: anti-A transferase antibodies reactive with gastric cancer tissue of type O individuals.

The expression of incompatible A carbohydrate antigens in some adenocarcinomas may provide an explanation for the generally observed lower incidence of adenocarcinoma among types O and B versus type A individuals. The chemistry and genetic basis of incompatible A expression is largely unknown. Here, we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed by enzyme analysis of extracts from the specimens. Blood group A carbohydrate antigens were also identified immunohistologically in these three cases as well as in five other cases. Thin-layer chromatography immunostaining analysis of glycolipid extracts from the three cases did not confirm the chemical presence of A antigen. The ABO genotype of all patients was found to be OO, showing that all carried O alleles with a structural defect at nucleotide position 261 leading to a shift in the reading frame. The data suggest that incompatible A antigen expression is a result of transferase expression derived from the ABO genes.

ABO Blood-Group System↗
PubMed1993

CDw75 antigen expression in human gastric carcinoma and adjacent mucosa.

BACKGROUND: The amount of sialic acid correlates with the invasiveness and metastasizing potential of several human tumors. The CDw75 epitope is a sialylated carbohydrate determinant generated by the beta-galactosyl alpha 2,6-sialyltransferase, which can be viewed as a target for identifying biologically aggressive tumors. METHODS: The authors performed an immunohistochemical study of CDw75 epitope expression in 87 cases of gastric carcinoma and adjacent mucosa and 331 metastases (329 lymph node metastases and 2 liver metastases) with the monoclonal antibody HH2. RESULTS: Normal-appearing mucosa, foci of intestinal metaplasia, and foveolar hyperplasia, adjacent to the carcinomas, were mainly nonimmunoreactive. Only a few parietal cells of the body mucosa were stained with HH2. Two of 12 cases with dysplasia showed CDw75 antigen expression in dysplastic glands. Forty-one cases (47.1%) were immunoreactive for CDw75 antigen in the primary tumors or metastases. A very close relationship was found between the expression of the antigen in primary tumors and their respective metastases. The expression of the antigen was correlated with an infiltrative growth pattern, lymphatic invasiveness, and aneuploidy. All but two immunoreactive cases had lymph node metastases or lymphatic permeation. No relationship was found between CDw75 antigen expression and the morphologic types of gastric carcinoma, amount of lymphoid infiltrate, vascular invasion, and penetration of the gastric wall. CONCLUSIONS: The authors conclude that CDw75 antigen expression can be used as a marker of malignant transformation of gastric epithelium and is a good indicator of the biologic aggressiveness of gastric carcinoma.

Aneuploidy↗
PubMed1993

Hyperplastic polyposis and diffuse carcinoma of the stomach. A study of a family.

BACKGROUND: The authors previously described a large pedigree with familial gastric polyposis and a high incidence of gastric cancer and demonstrated the autosomal dominant pattern of inheritance. The current study described the histologic and immunohistologic features of the lesions in an attempt to clarify the mechanisms underlying gastric carcinogenesis in this family. METHODS: The authors studied the histopathologic and histochemical features of several gastric specimens of nine members of this family and searched for the expression of carcinoembryonic antigen (CEA), p21 protein (ras oncogene), p53 protein (p53 suppressor gene), and simple mucin-type carbohydrate antigens (Tn, sialosyl-Tn, and T antigen before and after neuraminidase) and for the presence of Helicobacter pylori. RESULTS: The two carcinomas available for histologic revision were of the diffuse type. One of them apparently originated from a hyperplastic polyp. Hyperplastic polyps were diagnosed in five of seven patients without carcinoma. The remaining two patients had marked foveolar hyperplasia. Chronic atrophic gastritis with complete intestinal metaplasia (IM) was seen in three patients. p53 protein was not expressed in any of the cases. CEA and ras p21 oncoprotein were found in six and eight cases, respectively (mainly in hyperplastic foveolar epithelium). Tn, sialosyl-Tn, and T antigen were expressed in every case. H. pylori colonization was detected in all but the two patients with carcinoma. CONCLUSIONS: The authors concluded that foveolar hyperplasia/hyperplastic polyps play a key role in the development of diffuse carcinoma in this inherited polyposis, confined to the stomach, with hyperplastic phenotype. The genetic and environmental mechanisms underlying this particular situation remain to be clarified.

Adult↗
PubMed1993

Recurrent nephrotic syndrome after transplantation: early treatment with plasmaphaeresis and cyclophosphamide.

Steroid-resistant nephrotic syndrome (NS) with focal glomerulosclerosis (FGS) and its recurrence after transplantation are mainly seen in children. The recurrence rate approximates 30% and the graft loss is about half this. Several therapeutic regimens have been proposed, giving conflicting results. In an attempt to remove a putative circulating factor and inhibit its production by lymphocytes, three patients with biopsy-proven FGS in the native kidney were included in a prospective uncontrolled trial using early plasmaphaeresis followed by substitutive immunoglobulins in association with methylprednisolone pulses and cyclophosphamide instead of azathioprine over a 2-month period. The patients were girls, aged 6.5, 13.3 and 15.8 years, who received a cadaveric transplant; concomitant immunosuppression included prednisone and cyclosporine A. All three patients exhibited early recurrence of the NS and were treated 5-10 days after the onset of proteinuria. Rapid and sustained remission was achieved in all patients within 12-24 days on therapy. One patient experienced a late acute but steroid-sensitive rejection episode; another suffered from septic ankle arthritis as a complication of reinforced immunosuppression. The latter girl had a second late recurrence of proteinuria that was controlled within 7 weeks. With a 18- to 27-month follow-up, all three patients have normal renal function, normal blood pressure and no proteinuria. We conclude that intensive therapy using plasmaphaeresis, steroid pulses and cyclophosphamide over a 2-month period can induce complete remission in children with early recurrence of NS after transplantation.

Adolescent↗
PubMed1993

Purification of the integration host factor homolog of Rhodobacter capsulatus: cloning and sequencing of the hip gene, which encodes the beta subunit.

We describe a method for rapid purification of the integration host factor (IHF) homolog of Rhodobacter capsulatus that has allowed us to obtain microgram quantities of highly purified protein. R. capsulatus IHF is an alpha beta heterodimer similar to IHF of Escherichia coli. We have cloned and sequenced the hip gene, which encodes the beta subunit. The deduced amino acid sequence (10.7 kDa) has 46% identity with the beta subunit of IHF from E. coli. In gel electrophoretic mobility shift DNA binding assays, R. capsulatus IHF was able to form a stable complex in a site-specific manner with a DNA fragment isolated from the promoter of the structural hupSL operon, which contains the IHF-binding site. The mutated IHF protein isolated from the Hup- mutant IR4, which is mutated in the himA gene (coding for the alpha subunit), gave a shifted band of greater mobility, and DNase I footprinting analysis has shown that the mutated IHF interacts with the DNA fragment from the hupSL promoter region differently from the way that the wild-type IHF does.

Amino Acid Sequence↗
PubMed1993

[Neuroblastoma in children: clinical and biological aspects. An experience of screening in France].

Neuroblastoma is the commonest solid tumour in children under the age of 5 years (50% of cases before 2 years, 90% before 5) and the second cause of death after accidents. Approximately one child in 10,000 develops neuroblastoma by the age of 15 years. The situation in other European and North American countries is similar to that in France. As neuroblastoma is derived from the sympathetic nervous tissues, it is associated with the production of large amounts of catecholamines and their metabolites which are excreted in the urine. Less than 5% of cases do not produce catecholamines. Vanillylmandelic acid (VMA), homovanillic acid (HVA) and dopamine (DA) are the most useful chemical markers for the diagnosis and clinical control of neuroblastoma. They are generally measured using the reliable and sensitive high pressure liquid chromatography (HPLC). Survival is related to stage (the Evan's staging protocol has been superseded by the INNS staging), and age at diagnosis. There is almost 100% survival for stages I and IIa before the age of 12 months, and less than 20% for stage IV when diagnosed after 2 years of age. Multiple copies of the N-myc oncogene, deletions of chromosome 1p, and diploidy in tumour cells are associated with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

[Breaking the isolation. Telecommunication in the service of schooling of sick children].

We describe here a two-way teleconferencing system which links the sterile and pediatric units of the Center for Cancer Treatment in Lyon to a secondary school and the pediatric unit of the University Hospital Edouard-Herriot where primary teaching is given. Léon-Bérard Center and Edouard-Herriot Hospital are 300 m apart. Elie-Vignal secondary school is 6 km from the first site; all three institutes are connected through hyperfrequency aerials. With the help of this system, communication (voice and image) between children in hospital and pupils or teachers in school is instantaneous. Children in bed can listen to the lesson, break in on the conversation in school, ask questions or answer those of teachers. After school time, the system can also be used to organize games between children, or friendly contacts between children in each institute, children in the college, brothers, sisters or friends who may have access to one of those institutes. The system aims are: 1) to improve the education delivered to children and teenagers who spend long periods in hospital; 2) to establish a relationship between both worlds of healthy or sick children through teaching and playing in common; 3) finally, to facilitate the social insertion of sick children at leaving hospital.

Adolescent↗
PubMed1992

Immunohistochemical analysis of ras oncogene p21 product in human gastric carcinomas and their adjacent mucosas.

In an attempt to clarify the relationship between ras oncogene expression and the clinico-pathological features of malignant and pre-malignant lesions of the stomach we undertook the immunohistochemical study of the expression of ras gene p21 product in a series of eighty gastric carcinomas and their respective adjacent mucosas. In two cases the mRNA of Ha-ras was also studied by in situ hybridization. The majority of gastric carcinomas as well as their adjacent non-neoplastic mucosas expressed ras gene product. There was a significant relationship between the expression of ras gene p21 product and the morphologic pattern of the tumours. An enhanced ras expression was found in several conditions regarded as precursor lesions of intestinal and/or diffuse types of gastric carcinoma (dysplasia, foveolar hyperplasia and even the neck zone of normal-appearing gastric glands, namely in the mucosa adjacent to diffuse carcinomas). Ras expression was actually more prominent in most of these conditions than in their respective adjacent carcinomas. No significant relationship was found between ras expression and invasiveness of the wall, nodal metastases and venous invasion.

DNA, Neoplasm↗
PubMed1992

P53 mutations in gastric carcinomas.

We carried out an immunohistochemical study and DNA analysis of 30 gastric carcinomas to evaluate p53 overexpression and allelic loss at 17p. The immunohistochemical study demonstrated immunoreactivity for p53 protein in four cases. Allelic loss for the pYNZ22.1 marker was detected in nine cases. In total, ten cases showed immunoreactivity for p53 protein, allelic loss, or both. The study of nine of these cases by constant denaturant gel electrophoresis revealed p53 mutations in three cases. We conclude that the prevalence of mutations of p53 in our series is similar to what has recently been observed in other cases of gastric cancer, but lower than in colon carcinomas.

Alleles↗