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Biomedical subjects

J M Remy

Publications and source records attributed to J M Remy.

At least 19 recordsLinked to original sources
PubMed1997

A possible role for cathepsins D, E, and B in the processing of beta-amyloid precursor protein in Alzheimer's disease.

Formation of the 4-kDa peptides, which are essential constituents of the extracellular plaques in Alzheimer's disease, involves the sequential cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. The carboxy-terminal 99-amino-acid peptide which is liberated from APP by beta-secretase was used as a potential native substrate of the gamma-secretase(s). With the addition of an initiator Met and a FLAG sequence at the C-terminus (betaAPP100-FLAG), it was expressed in Escherichia coli under the control of the T7 promotor. The preferred site(s) of cleavage in the N-terminal 40-amino-acid beta-amyloid peptide and betaAPP100-FLAG by potential gamma-secretase(s) were rapidly identified using matrix-assisted laser-desorption/ionization time-of-flight mass spectroscopy in addition to peptide mapping followed by protein sequence analysis. Since gamma-secretases seem to be active at acidic pH, three cathepsins (D, E and B) were selected for testing. Studies using different detergents indicated that the cleavage preference of cathepsin D for the betaAPP100-FLAG is highly dependent on the surfactant used to solubilize this substrate. All three cathepsins were found to be capable of catabolizing both beta-amyloid peptides and the betaAPP100-FLAG. As cathepsin D was found to cleave the betaAPP100-FLAG in the vicinity of the C-terminus of the beta-amyloid peptides and cathepsin B has a high carboxypeptidase activity at low pH, the possibility cannot be excluded that cathepsins D and B are involved in the amyloidogenic processing of APP.

Alzheimer Disease↗
PubMed1995

Role of genetic factors in bronchial cancer. Based upon a case of anaplastic lung carcinoma in identical twins.

Having observed homozygotic identical twin brothers suffering simultaneously from anaplastic bronchial cancer leading rapidly to death in both cases, the authors assessed the frequency of such cases. The available literature failed to reveal any identical observations, although four cases of twins suffering from bronchial cancer featuring different histologies (three epidermoidal and one bronchiolar-alveolar) were noted. Statistics show that, in the area where the observed twins were living, anaplastic cancer occurs each year in 0.39% of 53-year-old men. The case of these twins therefore supports the idea of the role of genetic factors in the determination of bronchial cancer.

Bronchial Neoplasms↗
PubMed1995

Synthesis and comparison of tripeptidylfluoroalkane thrombin inhibitors.

Fluorinated ketone thrombin inhibitors based on the peptide sequence methyl-(D)-Phe-Pro-Arg-CF2R were synthesized: MDL 73,446 (1, R = F); MDL 73,775 (2, R = CF3); and MDL 75,579 (3, R = CH2CH2CH3). These were shown to be highly effective, slow binding inhibitors of thrombin. Anticoagulant activity was dose-dependent with 3 > 2 > 1 at doubling thrombin time and APTT, respectively. Anticoagulant activity corresponded with efficacy in a platelet-dependent (FeCl3-induced) rat carotid artery thrombosis model. Arterial occlusion was dose-dependently prolonged with 3 > 2 > 1 at doubling the occlusion time.

Amino Acid Sequence↗
PubMed1992

Rapid purification of the Aeromonas proteolytica aminopeptidase: crystallization and preliminary X-ray data.

The heat-stable aminopeptidase from Aeromonas proteolytica has been purified using two new procedures, with the aim of preparing large single crystals for X-ray analysis. In a first procedure, we tried to avoid any drastic conditions capable of inducing microheterogeneities in the protein sample. The enzyme was purified through two chromatographic steps based on hydrophobic interactions and ion exchange. In a second procedure a heat treatment of the protein to a temperature of 70 degrees C over 5 to 8 h was performed. Both procedures led to an electrophoretically homogeneous and crystallizable aminopeptidase; however, unexpectedly, the crystals obtained through the first procedure contained, in addition to the native aminopeptidase, a cleaved form of the enzyme which has been characterized. Only the native protein was present when the second procedure was used. Large crystals obtained with the native protein form, having an approximate size of 0.4 x 0.4 x 0.6 mm, produced an X-ray diffraction pattern that exhibited the symmetry associated with the hexagonal space group P6(1)22 (or its enantiomorph P6(5)22). The unit cell parameters were a = 109.1 A and c = 97.8 A. Assuming one molecule/asymmetric unit, a value of VM = 2.6 A3/Da and an approximate solvent content of 45% could be estimated. Measurable diffraction intensities were observed at a resolution of 2.5 A.

Aeromonas↗
PubMed1991

[Anti-hypertensive drugs prescribed to the elderly. Multicenter study at the hospital admission of 631 patients aged 70 plus years].

The anti-hypertensive treatment of 631 patients 70 years old and over was evaluated at the time of their hospitalization in 12 Internal Medicine departments in the western Paris suburbs, in May and June 1990. 49.6 +/- 3.9% received no such therapy; 30.3 +/- 3.6% were being treated for hypertension (group 1); 8.7 +/- 2.2% were taking anti-hypertensive drugs for poorly specified reasons (group 2); 11.4 +/- 2.5% were under such treatment for another reason. In groups 1 or 1 + 2, the most frequently prescribed medications were, in decreasing order: diuretics, calcium channel blockers, converting enzyme inhibitors, beta-blockers or central inhibitors. In the oldest patients, the beta-blockers were prescribed less and converting enzyme inhibitors more. More than half of the patients in groups 1 + 2 were taking a single drug. The most frequently prescribed combined therapy was diuretic + converting enzyme inhibitor. Our results seem to indicate that the prescription modalities depended, for the most part, upon an associated or suspected pathology, notably cardiac insufficiency.

Admitting Department, Hospital↗