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Biomedical subjects

M Lemoine

Publications and source records attributed to M Lemoine.

15 recordsLinked to original sources

A new population of very high energy gamma-ray sources in the Milky Way.

Very high energy gamma-rays probe the long-standing mystery of the origin of cosmic rays. Produced in the interactions of accelerated particles in astrophysical objects, they can be used to image cosmic particle accelerators. A first sensitive survey of the inner part of the Milky Way with the High Energy Stereoscopic System (HESS) reveals a population of eight previously unknown firmly detected sources of very high energy gamma-rays. At least two have no known radio or x-ray counterpart and may be representative of a new class of "dark" nucleonic cosmic ray sources.

Journal Article↗

High-energy particle acceleration in the shell of a supernova remnant.

A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays). The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT in the X-ray spectrum and later claimed as a source of high-energy gamma-rays of TeV energies (1 TeV = 10(12) eV). We present a TeV gamma-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.

Journal Article↗

Deficiency of molecular hydrogen in the disk of beta Pictoris.

Molecular hydrogen (H2) is by far the most abundant material from which stars, protoplanetary disks and giant planets form, but it is difficult to detect directly. Infrared emission lines from H2 have recently been reported towards beta Pictoris, a star harbouring a young planetary system. This star is surrounded by a dusty 'debris disk' that is continuously replenished either by collisions between asteroidal objects or by evaporation of ices on Chiron-like objects. A gaseous disk has also been inferred from absorption lines in the stellar spectrum. Here we present the far-ultraviolet spectrum of beta Pictoris, in which H2 absorption lines are not seen. This allows us to set a very low upper limit on the column density of H2: N(H2) </= 1018 cm-2. This non-detection is puzzling when compared to the quantity of H2 inferred from the infrared observations, but it does show that H2 is not in the disk on the direct line of sight. Carbon monoxide (CO) has been seen in absorption against the star, yielding a ratio of CO/H2 > 6 x 10-4. As CO would be destroyed under ambient conditions in about 200 years (refs 9, 11), our result demonstrates that the CO in the disk arises from evaporation of planetesimals.

Astronomical Phenomena↗

Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers.

BACKGROUND & AIMS: Cyclooxygenase (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins. Evidence suggests that nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer (CRC) and that this effect is mediated through COX inhibition. We analyzed and compared expression of the inducible COX-2 isoform in colorectal neoplasms from patients with hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and sporadic CRC. Given that COX-2 is induced by transforming growth factor (TGF)-beta and that TGF-beta type II receptor (RII) mutations are found in HNPCCs, we determined the relationship between RII status and COX-2 expression. METHODS: COX-2 protein expression was determined in colorectal epithelia using immunohistochemistry and Western blotting. Patients with HNPCC had known mutations in hMLH1 or hMSH2 genes and/or met the Amsterdam criteria. In CRCs from HNPCC cases, mutations were sought in the coding region of the RII gene using the polymerase chain reaction. RESULTS: COX-2 was detected in adenomas from 2 of 3 HNPCC, 6 of 7 FAP, and 5 of 8 sporadic cases. In CRCs, COX-2 staining was found in 16 of 24 (67%) HNPCC vs. 24 of 26 (92%) sporadic cases (P = 0.035) and in 2 of 2 FAP cases. Staining intensity was reduced in HNPCCs compared with sporadic CRCs (P = 0.035). Staining localized to the cytoplasm of neoplastic cells; normal epithelial cells were negative for COX-2. Overexpression of COX-2 in CRCs relative to normal mucosa was confirmed by Western blotting. TGF-beta RII mutations were detected in 12 of 14 HNPCCs examined, including 3 of 4 COX-2-negative and 9 of 10 COX-2-positive cancers. CONCLUSIONS: The frequency and intensity of COX-2 expression was significantly reduced in HNPCCs relative to sporadic CRCs, and was not a consequence of RII mutations. Given that many HNPCCs express COX-2, inhibition of this enzyme may be an important strategy to prevent CRC in these patients.

Adenomatous Polyposis Coli↗

Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinomas.

An imbalance between apoptosis and mitosis is believed to underlie colon cancer development and progression. These processes regulate the growth of normal and neoplastic epithelia, and in tumors, may confer prognostic information. To test this hypothesis, we determined apoptotic and mitotic indices (AI, MI) by morphology in H&E sections of 154 lymph node-negative, sporadic colon carcinomas. The relationship of these indices to genetic (p53 and Bcl-2) and biological features (DNA ploidy and cell kinetics) and patient survival rates was determined. Tumor features were compared in proximal and distal tumors, given postulated differences in their pathogenesis. Bcl-2 and p53 proteins were examined using immunohistochemistry and DNA ploidy and proliferative indices (PIs) by flow cytometry. Tumor features were dichotomized for analysis of relapse-free survival and overall survival (OS) rates using a Cox proportional hazards model. Median patient follow-up was 8.8 years. The median AI and MI were 1.2% (0-7.6) and 0.40% (0-1.8), respectively, and did not differ by tumor site. AI correlated with histological grade (P = 0.03); MI correlated with PI (P = 0.02) and inversely with Bcl-2 in distal tumors (P = 0.02). p53 and Bcl-2 expression were detected in 52 and 53% of tumors, respectively. Distal tumor site was associated with aneuploidy (P = 0.001), p53 (P = 0.001), and PI > 15% (P = 0.002). In a univariate analysis, colon cancers with high MIs (>0.5%) had a poor prognosis (P = 0.04). Bcl-2 overexpression (>20% + tumor cells) was associated with more favorable OS (P = 0.04). The association of ploidy and PI with outcome was of borderline significance for all tumors; however, diploidy predicted better survival in proximal cancers. In distal cancers, low AIs (< or = 0.25%) and high MIs (>0.5%) were adverse prognostic markers. After adjustment for other variables, an increased MI predicted shorter OS with a hazard ratio (HR) for death of 2.70; 95% confidence interval (CI) was 1.23-5.91 (P = 0.01). Expression of Bcl-2 was associated with more favorable OS (HR, 0.46; 95% CI, 0.21-1.0; P = 0.06). In proximal cancers, Bcl-2 expression was the most important predictor of OS (HR, 0.17; 95% CI, 0.03-0.85; P = 0.03). In distal tumors, low AIs (HR, 3.33; 95% CI, 1.27-9.09; P = 0.01) and high MIs predicted poor survival. In conclusion, increased mitosis and low or absent Bcl-2 expression are significant risk factors for death in node-negative colon cancers, as are low rates of apoptosis in distal tumors. If validated prospectively, our results may identify patient subsets than can benefit from adjuvant chemotherapy.

Adenocarcinoma↗

Sleep EEG and developmental dysphasia.

To determine the relation between developmental dysphasia and EEG anomalies during sleep, we compared 52 subjects with dysphasia with a control group of 20 children by using the ambulatory EEG method. Whereas 50% of the children with dysphasia experienced paroxysmal activity (PA), only two of the control group did. It is likely that paroxysmal abnormalities and language impairment are related to architectural dysplasia and neuron-migration disturbances. PA is frequent in subjects with receptive developmental dysphasia and may be the cause of language deterioration. When the occurrence of paroxysmal abnormalities during sleep is higher than 8% of total sleep time, we suggest the use of antiepileptic drugs.

Agnosia↗

Loss of p21WAF1/Cip1 protein expression accompanies progression of sporadic colorectal neoplasms but not hereditary nonpolyposis colorectal cancers.

p21 (p21WAF1/Cip1), a cyclin-dependent kinase inhibitor, induces G1 arrest and can inhibit the activity of the proliferating cell nuclear antigen (PCNA). We analyzed p21 expression during colorectal tumorigenesis, its association with its transcriptional regulator p53, and its relationship to rates of cell proliferation and apoptosis. p21 and p53 protein expression were examined in sporadic tumors and hereditary nonpolyposis colorectal cancers (HNPCCs) by immunohistochemistry (IHC) and immunoblotting. Apoptosis was examined using a DNA nick end-labeling assay, and cell proliferation was examined by PCNA staining. In normal colorectal epithelia, nuclear p21 staining was uniformly detected in crypt cells of the superficial compartment (upper one-third) that stained negatively for PCNA. p21 and PCNA expression were, therefore, mutually exclusive. In sporadic cases, a decrease in the frequency of p21 expression accompanied adenoma development and progression to carcinoma. Specifically, p21 was detected in 12 of 16 (75%) adenomas and 10 of 32 (31%) carcinomas. In contrast to sporadic cases, HNPCCs with known mutations in DNA mismatch repair genes expressed p21 in 12 of 15 (80%) carcinomas. An inverse relationship between p21 and p53 was observed wherein mutant p53 proteins were detected in 4 of 15 (27%) HNPCCs versus 22 of 32 (69%) sporadic carcinomas. Although p21+ carcinoma cells were generally negative for p53, IHC revealed that some carcinoma cells expressed both p21 and p53 proteins. Furthermore, p53-mutated SW480 colon carcinoma cells were found to coexpress p21 and p53, suggesting that p21 can also be activated by a p53-independent mechanism. No association was found between p21 or PCNA and apoptotic labeling indices in adenomas or carcinomas. In conclusion, a decrease in p21 expression accompanies neoplastic progression in sporadic cases but not in HNPCCs. This finding appears related to p53 status in that the frequency of p53 expression was significantly reduced in HNPCCs compared to sporadic cases, suggesting a difference in their molecular pathways of tumorigenesis.

Colorectal Neoplasms↗

A high deuterium abundance at redshift z = 0.7.

Of the light elements, the primordial abundance of deuterium relative to hydrogen, (D/H)p, provides the most sensitive diagnostic for the cosmological mass density parameter, omegaB. Recent high-redshift D/H measurements are highly discrepant, although this may reflect observational uncertainties. The larger primordial D/H values imply a low omegaB (requiring the Universe to be dominated by non-baryonic matter), and cause problems for galactic chemical evolution models, which have difficulty in reproducing the steep decline in D/H to the present-day values. Conversely, the lower D/H values measured at high redshift imply an omegaB greater than that derived from 7Li and 4He abundance measurements, and may require a deuterium-abundance evolution that is too low to easily explain. Here we report the first measurement of D/H at intermediate redshift (z = 0.7010), in a gas cloud selected to minimize observational uncertainties. Our analysis yields a value of D/H ((2.0 +/- 0.5) x 10[-4]) which is at the upper end of the range of values measured at high redshifts. This finding, together with other independent observations, suggests that there may be inhomogeneity in (D/H)p of at least a factor of ten.

Astronomical Phenomena↗