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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
PubMed1996

Granular cell tumour and leiomyomatosis of the esophagus--a non-coincidental association?

One case of esophageal granular cell tumour (GCT) associated with diffuse leiomyomatosis of the distal esophagus is presented. The rarity of each of the lesions per se raises the possibility that the association between GCT and diffuse leiomyomatosis, a previously unreported finding, is not coincidental. In view of the present knowledge on both conditions we suggest that an underlying genetic alteration may be responsible for the hereby described association.

Esophageal Neoplasms↗
PubMed1995

Increasing levels of MYC and MET co-amplification during tumor progression of a case of gastric cancer.

The cytogenetic study of a nodal metastasis from a gastric carcinoma, after two passages in nude mice, revealed a large number of double minutes. Comparative genomic in situ hybridization (CGH) analysis using DNA extracted from this xenograft revealed the existence of three clear amplification units that originated from the chromosomal subregions 6q24-25, 7q31-32, and 8q24 in the xenograft DNA. Similar, though less prominent, CGH results were found with DNAs extracted from the primary tumor and its metastasis, implying that the same amplicons were also present, albeit less abundantly, in the DNAs of these neoplastic tissues. Southern analysis of the second-passage xenograft detected 18- and 10-fold amplification of MET (located at 7q31) and MYC (located at 8q24), respectively. The retrospective study of the first passage of the xenograft, as well as of the metastatic and primary tumors before xenografting, showed amplification levels of MET of, respectively, 12-, 9-, and 5-fold and MYC of, respectively, 8-, 7-, and 5-fold. Our results suggest that increased levels of co-amplification of MYC and MET correlate with enhanced growth potential in this case of gastric carcinoma.

Adult↗
PubMed1995

Substrate dependence of amiloride- and soman-induced conformation changes of butyrylcholinesterase as evidenced by high-pressure perturbation.

Previous results on butyrylcholinesterase-catalyzed hydrolysis of o-nitrophenylbutyrate in the presence of soman, an irreversible inhibitor of cholinesterases, suggested that reversible binding of soman preceding enzyme phophonylation induced a new enzyme conformational state (E'). The purpose of the present study was to determine whether this effect depends on soman itself or is dependent on the presence and nature of substrate or ligand. First, we examined the effect of amiloride, a reversible cholinesterase effector, upon the butyrylcholinesterase-catalyzed hydrolysis of nitrophenyl esters. The effect of amiloride was found to be dependent on the position ortho or para of the substrate nitro group: amiloride acts as a non-linear reversible activator of p-nitrophenyl ester hydrolysis and as a non-linear reversible inhibitor of o-nitrophenyl ester hydrolysis. Second, the effect of amiloride upon hydrolysis of o/p-nitrophenylbutyrate was also studied under perturbing conditions, i.e., as a function of pressure (1-1600 bar) in the presence and absence of soman. Results show that the effect of reversible soman binding on butyrylcholinesterase activity in the presence of amiloride depends on the position of the substrate nitro group and amiloride concentration. Molecular modelling suggests that the presence of amiloride determines the orientation of ortho- and para-nitrophenyl esters in the active-site. gorge. The nitro group of o-nitrophenylbutyrate interacts with the oxyanion hole via hydrogen bonds and its phenyl ring interacts with amiloride whose heterocycle faces Trp-82. The nitro group of p-nitrophenylbutyrate does not interact with the oxyanion hole but points towards Tyr-332; the phenyl ring of p-nitrophenylbutyrate interacts with amiloride but there is no steric constraint on the acyl chain. Thus, the network of interactions in ternary complexes is tighter with o-nitrophenylbutryate as the substrate. There is no evidence for the existence of amiloride and/or soman-induced E' state when p-nitrophenylbutyrate is the substrate. On the other hand, reversible binding of amiloride and/or soman induces new active conformational states that may be either binary (or ternary) enzyme-ligand complex or new free enzyme conformation resulting from long-lived ligand-induced enzyme conformational change when o-nitrophenylbutyrate is the substrate. These ligand-induced states are stabilized by high pressure.

Amiloride↗
PubMed1995

Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile.

Mutations in recently identified genes on chromosomes 2 and 3 seem to be responsible for repair errors (RER+) throughout the genome. This novel genetic mechanism was first reported in hereditary non-polyposis colorectal cancer syndrome and in cancers that are characteristic of this syndrome, such as carcinomas of the right colon, stomach and endometrium. We investigated the frequency of RER+ phenotype in a series of 34 sporadic gastric carcinomas, in an attempt to see if the RER+ cases displayed any particular morphologic features and/or if they showed distinctive clinicopathologic characteristics. Twelve loci were investigated. We found 23 RER- cases (67.6%) and 11 RER+ cases (32.4%). A significant association was found between RER+ carcinomas and localization of the tumors: 9 of the 11 RER+ carcinomas (81.8%) were located at the antrum whereas all the cardiac tumors were RER-. The RER+ phenotype was also significantly related to the presence of moderate/abundant T-cell lymphoid infiltration within the tumors. The 3-year survival rate of patients with RER+ tumors was suggestively longer than that of patients with RER- tumors. No significant relationship was found between several clinicopathologic characteristics of the cases, including age, sex, staging, histologic type and ploidy, despite a trend towards an association between RER+ phenotype and advanced age of the patients and poorly differentiated, intestinal type of the carcinomas. The high frequency of microsatellite instability in sporadic gastric carcinomas supports the involvement of this genetic mechanism in gastric carcinogenesis. Gastric carcinomas with the RER+ phenotype tend to occur as poorly differentiated adenocarcinomas in the antrum of elderly patients, display abundant T-cell infiltration and carry a relatively good prognosis.

Adult↗
PubMed1995

[Bacterial complications of nephrotic syndrome in children].

OBJECTIVES: Evaluate bacterial infection epidemiology and pathophysiology in children with nephrotic syndrome. METHODS: From January 1983 to December 1992, 399 children with the nephrotic syndrome were admitted in 3 University Pediatric wards (Paris Enfants Malades, Lyon Edouard Herriot, Lyon Debrousse). Severe bacterial infection was diagnosed when the patient's condition has justified an intravenous antibiotherapy. RESULTS: Forty-eight bacterial infections were noted in 32 patients (8%); the infection was the first symptom of the disease in 10 patients (31%); one patient died shortly after admission. Severe bacterial infection concerned steroid-resistant nephrotic syndrome in 13 cases (41%), but only 7 out of them received immunosuppressive agents at the time of the infection. Eleven children (34%) experienced recurrent infections (1 to 6 recurrences), several of which under antibioprophylaxy. Half of the infections involved peritonitis and 50% of the identified germs were S. pneumoniae. However, peritonitis was not always related to S. pneumoniae (1 H. influenzae among 9 identified germs). CONCLUSIONS: These data demonstrate the importance of microbiological sampling and justify a first-line antibiotherapy using a third generation cephalosporin. The presentation of severe bacterial infections show that it is less a iatrogenic event than a consequence of immunological disturbances induced by the nephrotic syndrome itself, as suggested by the acquired deficiency of factor I and B. Despite recent advances in antibiotic strategies responsible for a significant reduction in the severity of such infections (1 death among 32 patients), preventive treatments are quite disappointing.

Adolescent↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

[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↗
PubMed1994

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↗
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↗