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Biomedical subjects

L David

Publications and source records attributed to L David.

At least 91 records · Page 5Linked to original sources

Epinigericin toxicity towards Tetrahymena pyriformis GL; changes in cell volume and intracellular pH.

A study of the toxicity of epinigericin, an antibiotic ionophor, towards the ciliate Tetrahymena pyriformis showed that this molecule stopped cell division, increased cell volume and led to a more basic intracellular pH. The action of epinigericin was probably linked to its function as an ionophor. The ionic selectivity of this molecule is still not known. The raising of the intracellular pH of ciliates by this antibiotic may be linked to its toxic action and its iontransport mechanism in Tetrahymena.

Animals↗

Biosynthetic study on the polyether carboxylic antibiotic, nigericin production and biohydroxylation of grisorixin by nigericin-producing Streptomyces hygroscopicus NRRL B-1865.

With addition of methyl oleate, the increased yield of antibiotic production by nigericin-producing Streptomyces hygroscopicus NRRL B-1865 also resulted in the isolation of three additional polyether antibiotics. Two of these are abierixin and epinigericin, as new antibiotics. The third antibiotic is grisorixin. The production of both abierixin (opened ring A and 30-CH2OH) and grisorixin (ring A and 30-CH3) poses the problem of the identity of the last pathway precursor of the major metabolite, nigericin (ring A and 30-CH2OH). Transformation experiments of abierixin by S. hygroscopicus gave negative results. Hydroxylation of grisorixin to nigericin by S. hygroscopicus represents the final step in nigericin biosynthesis.

Anti-Bacterial Agents↗

[Tubo-petrous fistula with valve: apropos of a case].

The abnormal pneumatization of the apex of the petrous bone may determine pathological disturbances in the existing conditions of a tube-petrous fistula with valve. Such a clinical case is presented with tube-petrous fistula, which during a period of four years was investigated in several clinics due to its non-typical clinical symptoms, without the diagnostic or treatment having been mentioned. The authors insisted that the Eustachian tube should be investigated in order to establish a probable diagnostic. The paper presents the technique of operation used, the injuries found and the manner of obturating the fistula in two successive surgical operations.

Adult↗

p53 alterations in gastric carcinoma: a study of 56 primary tumors and 204 nodal metastases.

We have looked for LOH, mutation, and expression of p53 in a series of 56 primary gastric carcinomas, using Southern blotting, constant denaturant gel electrophoresis (CDGE), direct sequencing, and immunohistochemistry. Two hundred-four lymph node metastases from 36 of these cases were also studied by immunohistochemistry. Loss of constitutional heterozygosity for the p53 locus was detected in five of 16 informative cases; in four of these cases there was a concurrent point mutation at the retained allele. Immunoreactivity for p53 product and mutation of p53 were observed in nine and 10 of the 56 tumors, respectively. There was no significant relationship between p53 immunoreactivity or mutation and pathologic features. The overall prevalence of p53 mutations, as detected by CDGE, was 18%. Direct sequencing confirmed p53 mutations (all G:C-A:T transitions) in seven cases, six of which were missense mutations; the remaining case was a silent mutation. In three of the cases with missense mutations, these occurred at CpG dinucleotides (codons 175, 273, and 282). Three cases with immunoreactivity for p53 product in the primary tumor also showed positive staining in the metastases. In two of these cases (with six and nine metastases, respectively) a positive staining was observed in all lymph node metastases, whereas in the remaining case only two of four nodal metastases were positively stained. In no single case was a positive staining observed in a metastasis where the primary tumor gave a negative staining result. Five of the six cases with p53 mutations and fresh material available for cell culture were successfully grown in vitro and all had abnormal karyotypes.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗