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Biomedical subjects

L David

Publications and source records attributed to L David.

At least 73 records · Page 4Linked to original sources
PubMed1994

Expression of laminin, collagen IV, fibronectin, and type IV collagenase in gastric carcinoma. An immunohistochemical study of 87 patients.

BACKGROUND: This study attempted to determine if there is a pattern of matrix/matrix-degrading-enzyme immunoreactivity related to the morphologic types of gastric carcinoma or to their invasiveness. METHODS: The authors performed an immunohistochemical study of the basement membrane antigens laminin and collagen IV, fibronectin, and Type IV collagenase in a series of 87 gastric carcinomas and their respective nodal metastases (n = 329). RESULTS: Laminin expression was observed almost exclusively in carcinomas of the intestinal type. The expression of collagen IV was significantly higher in intestinal (52%) and atypical (44%) carcinomas than in diffuse (10%) carcinomas; collagen IV expression also was significantly correlated with lymphatic invasion and aneuploidy. Ninety percent of the carcinomas expressed fibronectin, mostly in the connective tissue at the invading edge of the tumors; fibronectin expression was significantly related to the expanding growth pattern of the neoplasms. Eighty-six percent of the tumors expressed Type IV collagenase, regardless of the histologic type or invasive properties. No relationship was observed between the expression of any of the antigens and the S-phase fraction of the tumors. No significant differences were found between the immunohistochemical profile of the primary tumors and their metastases. CONCLUSIONS: The authors conclude that the expression of basement membrane antigens is related to the type of gastric carcinomas, rather than the cell differentiation or proliferative activity of the tumors. The putative prognostic meaning of the relationship between collagen IV immunoreactivity and aneuploidy and lymphatic invasiveness of the carcinomas remains to be clarified.

Carcinoma↗
PubMed1994

Toxoplasma gondii: activity of the polyether ionophorous antibiotic nigericin on tachyzoites in cell culture.

Polyether ionophorous antibiotics are widely used prophylactically to prevent coccidiosis in livestock production. The study of the effects of the nigericin on tachyzoites of Toxoplasma gondii clearly demonstrated that very low concentrations of this ionophore (0.05 microgram/ml) were sufficient to inhibit strongly the penetration and totally inhibit the intracellular development of parasites. Both nigericin and epinigericin showed a similar activity against tachyzoite development. However, the activity of abierixicin was 50-fold lower. Such antibiotic concentrations did not seem to affect host cells. Immunofluorescence and electron microscopy showed important changes in the cytology of the antibiotic-treated parasites: they were vacuolated or swollen and were sometimes found burst open, having lost their original shape. The magnitude and the frequency of alterations rose as concentrations in ionophore increased.

Animals↗
PubMed1994

The IHF proteins of Rhodobacter capsulatus and Pseudomonas aeruginosa.

The binding properties of the two IHF consensus sequences present in the promoter region of the hydrogenase structural operon, hupSL, of Rhodobacter capsulatus were studied by gel retardation assays using the heterodimeric IHF-like proteins isolated from R capsulatus, from Pseudomonas aeruginosa and from Escherichia coli. The three IHF proteins bound preferentially to the IHF consensus proximal to hupS. The three-dimensional structure of R capsulatus IHF was modeled using a computer-based amino acid replacement strategy and the known coordinates of crystallized HU protein (HBS) from Bacillus stearothermophilus. Double-stranded DNA and the interaction of IHF and DNA were then modeled using the molecular modeling package Quanta 3.3, and taking into account foot-printing data obtained with IHF-DNA complexes and the fact that the replacement of Arg8 by Cys8 in the alpha subunit, the product of himA, renders R capsulatus IHF ineffective in the activation of hydrogenase synthesis. In this model, IHF is shown to interact with DNA bent by 140 degrees, and Arg8 of HimA capable of interacting with the phosphate-ribose backbone of DNA in the flanking region of the IHF binding site.

Amino Acid Sequence↗
PubMed1994

Bone mineral density after renal transplantation in children.

Longitudinal bone mineral changes after renal transplantation were studied in 14 children aged 8 +/- 4 years. Combination immunosuppressive therapy was given to all patients (prednisone, azathioprine, cyclosporine). Bone mineral density (BMD) measurements of the first through fourth lumbar vertebrae by dual-energy X-ray absorptiometry were performed within 1 year preceding renal transplantation and 6, 12, and 24 months afterward (M0, M6, M12, and M24, respectively). The results of BMD obtained in grams of hydroxyapatite per square centimeter of spine projected area were subsequently transformed to standard deviation scores for a normal pediatric population. In addition, we used a mathematical spine volume correction to give the results in grams per cubic centimeter. All patients had a well-functioning renal graft at M6, M12, and M24 and a normal serum creatinine level. Significant decreases in BMD, standard deviation score, and spine volume-corrected BMD were observed 6 months after renal transplantation (p < 0.05, p < 0.01, and p < 0.01 respectively); the median loss of BMD and spine volume-corrected BMD was 9.2% and 15.6% at M6, respectively, and the median serum parathyroid hormone level dropped from 125 to 34 pg/ml. Between M6 and M12, BMD increased significantly up to 95% (median) of pretransplantation values and reached 97.2% (median) at M24. Similar but less marked improvement was observed in spine volume-corrected BMD results, reaching 87.7% and 87.4% at M12 and M24, respectively. A negative correlation was found between the cumulative prednisone dose and BMD in grams per square centimeter at M6 (r2 = 0.603; p = 0.006), M12 (r2 = 0.532; p = 0.015), and M24 (r2 = 0.40; p = 0.014). There was no correlation between cumulative prednisone dose and spine volume-corrected BMD or standard deviation score. Mean 6-month cyclosporine levels did not correlate with any measure of BMD. We conclude that after renal transplantation children have a significant decrease of BMD during the first 6 months after the operation, despite normal graft function and growth improvement.

Absorptiometry, Photon↗
PubMed1994

T (Thomsen-Friedenreich) antigen and other simple mucin-type carbohydrate antigens in precursor lesions of gastric carcinoma.

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn,sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.

Adenocarcinoma↗
PubMed1994

Papillary necrosis and medullary sponge kidney in a patient with hemoglobin SC.

A 22-year-old woman with hemoglobin SC who was hematologically asymptomatic, developed gross hematuria associated with urinary tract infection, without any urological antecedents. Investigations revealed a unilateral hematuria due to papillary necrosis on the left kidney. Medullary sponge kidney was also discovered by radiologic investigations. Papillary cysts could play a role in the occurrence of papillary necrosis.

Adult↗
PubMed1994

[Exophthalmos in children caused by vascular orbital neoformation].

BACKGROUND--Exophthalmos or proptosis may be a result of several causes; when unilateral, it leads to search a variety of orbital tumors. CASE 1--A 2 month-old baby presented with a right exophthalmos which developed within a few days. Computed tomography showed infiltration of the orbit by a mass. Surgical biopsy showed capillary hemangioma. The patient was given prednisone 2 mg/kg/day for 2 months; exophthalmos disappeared within 10 days and the child was normal 7 years later. CASE 2--A 13 year-old boy was examined because he had developed left exophthalmos within 2-3 weeks. Ultrasonography and computed tomography showed an orbital tumor compressing the eye and the optic nerve. This tumor was excised and histological examination showed that it was a thrombotic arterial aneurysm. CONCLUSIONS--Vascular lesions can be responsible for a rapidly developing orbital tumor. Their diagnosis can be difficult and must be made in order to avoid aggressive surgery.

Adolescent↗
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↗