Biomedical subjects

N Sturm

Publications and source records attributed to N Sturm.

8 recordsLinked to original sources

PubMed2006

Longitudinal evaluation of a fibrosis index combining MMP-1 and PIIINP compared with MMP-9, TIMP-1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon-alpha and ribavirin.

We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients.

Adult↗

PubMed2004

[Pelvic muscular metastasis of well differentiated thyroid carcinoma].

Authors report on a case of one intramuscular metastasis from a non-medullary differentiated thyroid carcinoma. Muscular metastasis are rare in this pathology. Moreover, body-scanning scintigraphic interpretation is difficult for the pelvic area. False-positive are numerous and a very precise topographical diagnosis is required to choose the best surgical approach. Authors propose a specific management of different imaging methods for such a metastatic site. They associate a CT scan and a multiplanar iodine and technetium scintigraphy.

Adenocarcinoma, Follicular↗

PubMed2003

34BetaE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma.

AIMS: Monoclonal antibody 34betaE12 (Ck34betaE12) recognizes a set of cytokeratins (1, 5, 10, 14) expressed in normal stratified squamous epithelium. We have recently reported its expression in squamous cell carcinoma and basaloid carcinoma, in contrast to large cell neuroendocrine carcinoma, an entity with overlapping morphological features with basaloid carcinoma. We have now examined the role of Ck34betaE12 in discriminating between neuroendocrine and non-neuroendocrine proliferations. METHODS AND RESULTS: We performed an immunohistochemical study of 228 cases, comprising the whole spectrum of lung neuroendocrine proliferations and tumours. All cases of neuroendocrine cell hyperplasia (n = 15), tumorlet (n = 23), typical carcinoid (n = 27) and atypical carcinoid (n = 23) were completely negative for Ck34betaE12. Although the neuroendocrine cells of small cell lung carcinoma and large cell neuroendocrine carcinoma were consistently negative, a strong and diffuse positive staining was found in the non-neuroendocrine components of combined small cell carcinoma (three of eight cases) and combined large cell neuroendocrine carcinoma (11 of 12 cases). In addition, scattered Ck34betaE12+ cells were noted in 11 of 64 (17%) large cell neuroendocrine carcinoma and in seven of 56 (12.5%) small cell carcinoma, which were not obviously histologically combined. This heterogeneity of high-grade neuroendocrine tumours was not observed in carcinoids which lack Ck34betaE12 clusters of reactive cells. There was mutual exclusion between expression of neuroendocrine markers and that of Ck34betaE12. CONCLUSION: We conclude that 34betaE12 expression excludes the neuroendocrine nature of tumour cells and uncovers the real frequency of combined forms in high-grade neuroendocrine tumours.

Biomarkers, Tumor↗

PubMed2001

Thyroid transcription factor 1 and cytokeratins 1, 5, 10, 14 (34betaE12) expression in basaloid and large-cell neuroendocrine carcinomas of the lung.

Basaloid carcinoma (BC) and large-cell neuroendocrine carcinoma (LCNEC) are 2 recently recognized variants of large-cell lung carcinomas that may overlap in their morphology, and are discriminated by expression of neuroendocrine markers in LCNEC. Because thyroid transcription factor 1 (TTF-1) is expressed in lung adenocarcinomas but not in squamous cell carcinomas (SCC), and 34betaE12 recognizes a set of high-molecular-weight cytokeratins characteristic of basal stem cells, we hypothesized that these 2 markers could help in distinguishing BC from LCNEC. Immunostaining for TTF-1 was detected in 40.9% of pure LCNEC but in no BC or basaloid variant of SCC. In contrast, immunoreactivity for 34betaE12 was shown in all BC and basaloid variant of SCC but in only 1 LCNEC. Bouin fixation was less efficient than formalin in the immunodetection of both markers for its well-known deleterious effect on antigen preservation. Specificity of TTF-1 for LCNEC (100%) and that of 34betaE12 for BC (98.3%) exceeded that of NE markers for distinction of these 2 entities. These data show that TTF-1 and 34betaE12, in association with specific neuroendocrine markers, represent a useful panel of antibodies in differentiating carcinomas presenting with a solid pattern, palisading, or pseudorosettes, the expression of TTF-1 excluding the diagnosis of BC, and staining with 34betaE12 excluding pure LCNEC.

Carcinoma, Large Cell↗

PubMed2000

NCAM (neural cell adhesion molecules) expression in malignant mesotheliomas.

Neural cell adhesion molecules (NCAM) are adhesion molecules expressed by neural and neuroendocrine tumors and a few biphasic tumors such as synovialosarcomas and breast phyllode tumors. To investigate NCAM expression in mesotheliomas, we studied 26 cases of epithelioid (n = 12), biphasic (n = 11), and sarcomatoid (n = 3) malignant mesotheliomas (MM), in comparison with normal mesothelium, and 50 primary non-small cell lung carcinomas (NSCLC) (25 adenocarcinomas [ADC] and 25 squamous cell carcinomas [SCC]), using electron microscopy as a gold standard for recognition of MM. NCAM reactivity using 123C3 antibody was compared with that of NE markers such as chromogranin A and synaptophysin. Although normal mesothelium remains negative, NCAM was expressed in 19 of 26 MM (73%) with a membranous staining on frozen or paraffin sections. In 6 of 12 epithelioid MM, the tumor cells expressed NCAM, whereas in 5 cases stromal fibroblasts showed a strong but focal staining. In 11 biphasic MM, 4 presented an NCAM reactivity of both epithelioid and spindle cell components, whereas in 7, only fusiform component was NCAM positive. Two of 3 sarcomatoid MM showed an NCAM expression. Chromogranin expression was never seen, whereas synaptophysin was noticed in 2 cases. No case of NSCLC showed membranous 123C3 staining, whereas 2 ADC weakly expressed synaptophysin. We conclude that NCAM expression in MM is reminiscent of its expression in mesoderm during fetal life and consistent with that reported in other biphasic tumors. These data show that NCAM expression occurs in 73% of MM, highly exceeding that observed in lung cancer.

Adenocarcinoma↗

PubMed2000

Divergent differentiation in neuroendocrine lung tumors.

The classification of neuroendocrine (NE) lung tumors has been revised in the 1999 World Health Organization (WHO) classification of lung tumors, allowing sharp morphological definition of typical versus atypical carcinoids, and atypical carcinoids versus large cell neuroendocrine carcinoma (LCNEC), a newly described class of high-grade NE lung tumors which differs from small-cell lung cancer by a large-cell phenotype. Divergent differentiation accounts for the high frequency of glandular differentiation with mucin production, and ultrastructural features in carcinoids and LCNEC, and low frequency of squamous differentiation in both LCNEC and SCLC. Specific NE markers (chromogranin, synaptophysin, neural cell adhesion molecule) and epithelial markers consistently negative in neuroendocrine components (cytokeratins 1, 5, 10, 14; epidermal growth factor (EGF)-receptor, human leukocyte antigen beta 2 (HLA-beta2) microglobuline) help to recognize divergent differentiation in NE tumors. At morphological level, divergent differentiation in NE tumors is recognized in WHO classification as variants: combined SCLC and combined LCNEC. The derivation of all lung tumors from a common endodermal stem cell and adoption of amine precursor uptake and decarboxylation properties by this endodermal stem cell explains divergent differentiation in NE lung tumors and the occurrence of NE subsets in NSCLC.

Biomarkers, Tumor↗

PubMed1996

Effects of a 33 residue interleukin-1 beta peptide and the antioxidant PQQ on interleukin-1 beta-mediated inhibition of glucose-stimulated insulin release from cultured mouse pancreatic islets.

Interleukin-1 beta (IL-1 beta) significantly inhibits insulin secretion from glucose stimulated islet cells. The mechanism for this inhibition has been hypothesized to be due to stimulation of the inducible form of nitric oxide synthase and a resulting increase in nitric oxide (NO) concentration. Ways to block the effect of IL-1 beta have focused on blocking the binding of IL-1 beta to the IL-1 receptor and the use of antioxidants to neutralize increases in NO. This report focuses on a 33 residue peptide synthesized based on the C-terminal region of the IL-1 beta molecule, a reported binding site of the IL-1 beta molecule, and the redoxcycling antioxidant pyrroloquinoline quinone (PQQ). The 33 residue peptide did not function as an antagonist, but as a weak agonist. High concentrations of PQQ itself inhibited glucose-dependent insulin release while low concentrations did not. PQQ had no effect on the actions of IL-1 beta. Three isosteric and isomeric analogues of PQQ were also investigated. One of the PQQ isomers had an inhibitory effect on insulin secretion at low concentrations where PQQ had no effect. These results reflect the sensitivity of islets to oxidative stress.

Amino Acid Sequence↗

PubMed1992

Computer methods for locating kinetoplastid cryptogenes.

RNA editing in the mitochondria of kinetoplastid protoza involves the insertion and/or deletion of precise numbers of uridine residues at precise locations in the numbers of uridine residues at precise locations in the transcribed RNA of certain genes. These genes are known as cryptogenes. In this paper we study computational algorithms to search for unknown cryptogenes and for the associated templates for insertion of uridines, gRNA sequences. The pairwise similarity search algorithm of Smith and Waterman (1) is modified to study this problem. The algorithm searches for unknown gRNAs given the cryptogene sequence. The method is tested on 4 known cryptogenes from L.tarentolae which are known to have 7 associated gRNAs. The statistical distribution of the longest gRNA when comparing random sequences is derived. Finally we develop an algorithm to search for cryptogenes using amino acid sequences from related proteins.

Algorithms↗