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Biomedical subjects

M Samson

Publications and source records attributed to M Samson.

At least 37 records · Page 2Linked to original sources
PubMed1996

A dual-tropic primary HIV-1 isolate that uses fusin and the beta-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors.

Here, we show that the beta-chemokine receptor CKR-5 serves as a cofactor for M-tropic HIV viruses. Expression of CKR-5 with CD4 enables nonpermissive cells to form syncytia with cells expressing M-tropic, but not T-tropic, HIV-1 env proteins. Expression of CKR-5 and CD4 enables entry of a M-tropic, but not a T-tropic, virus strain. A dual-tropic primary HIV-1 isolate (89.6) utilizes both Fusin and CKR-5 as entry cofactors. Cells expressing the 89.6 env protein form syncytia with QT6 cells expressing CD4 and either Fusin or CKR-5. The beta-chemokine receptors CKR-3 and CKR-2b support HIV-1 89.6 env-mediated syncytia formation but do not support fusion by any of the T-tropic or M-tropic strains tested. Our results suggest that the T-tropic viruses characteristic of disease progression may evolve from purely M-tropic viruses prevalent early in virus infection through changes in the env protein that enable the virus to use multiple entry cofactors.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Cloning and tissue distribution of the human P2Y1 receptor.

Sets of degenerate oligonucleotide primers synthesized on the basis of the best conserved regions of the chick brain P2Y/P2Y1 and the murine neuroblastoma P2U/P2Y2 receptors were used in polymerase chain reaction experiments on human genomic DNA. An amplified fragment of 712 base pairs was then used as a probe to screen a human genomic DNA library. Several clones were isolated and sequencing revealed an intronless 1122 base pair open reading frame. The corresponding amino acid sequence revealed 83% identity with the chick brain P2Y1 receptor and 34% with the murine neuroblastoma P2Y2 receptor. In COS-7 cells transfected with the coding sequence inserted into the pcDNA3 expression vector, 2-methylthioATP and ATP produced a strong stimulation of inositol phosphates, a typical response of a P2Y1 receptor. Northern blot analysis detected a 6.7 kilobase messenger RNA in most human tissues, the strongest signals being observed in prostate and ovary.

Amino Acid Sequence↗
PubMed1996

Molecular cloning and functional expression of a new human CC-chemokine receptor gene.

The cloning of several receptors activated by either CC or CXC chemokines and belonging to the G protein-coupled family of receptors has been reported recently. In the present work, we describe the cloning of a human gene, named ChemR13, encoding a new CC-chemokine receptor. The gene encodes a protein of 352 amino acids with a calculated molecular mass of 40 600 Da and displaying a single potential site for N-linked glycosylation. Using a set of overlapping lambda clones, the genomic organisation of the locus was investigated, demonstrating that the ChemR13 gene is physically linked, and in the same orientation, as the CC-CKR2 gene that encodes a receptor for the monocyte chemoattractant protein-1 (MCP-1). A distance of 17.5 kb separates the two coding regions, which share 75% identity in nucleic acid and amino acid sequences. Human ChemR13 was functionally expressed in a stably transfected CHO-K1 cell line. Physiological responses to chemokines were monitored using a microphysiometer. Macrophage inflammatory protein 1 alpha (MIP-1 alpha) was the most potent agonist. MIP-1 beta and RANTES were also active at physiological concentrations. The other CC-chemokines, MCP-1, MCP-2 and MCP-3, as well as CXC-chemokines (IL-8, GRO alpha) had no effect. ChemR13 receptor transcripts were detected by Northern blotting in the promyeloblastic cell line KG-1A, suggesting a potential role in the control of granulocytic lineage proliferation or differentiation. ChemR13 is thus a new member of the growing family of chemokine receptors that mediate the recruitment of cells involved in immune and inflammatory processes. Being the fifth functionally identified receptor in his class, this new CC-chemokine receptor (CC-CKR) is tentatively designated CC-CKR5.

Amino Acid Sequence↗
PubMed1996

Molecular cloning and chromosomal mapping of a novel human gene, ChemR1, expressed in T lymphocytes and polymorphonuclear cells and encoding a putative chemokine receptor.

We describe the cloning of a human gene, named ChemR1, encoding a new putative chemokine receptor sharing 48% identity with CC-chemokine receptor (CCR)4 and 44% identity with CCR1. It displays four extracellular cysteines that are conserved among all other chemokine receptors. ChemR1 transcripts were detected by Northern blotting in the T lymphoblastic cell lines Jurkat and MOLT-4, but not in the pre-B lymphoblastic cell line JM-1. ChemR1 receptor transcripts were also detected by reverse transcription and polymerase chain reaction analysis in unstimulated CD4+ and CD8+ T cells and polymorphonuclear cells prepared from peripheral blood. The chromosomal localization was performed by radiation hybrid mapping and testing of a panel of yeast artificial chromosome clones. This allowed the assignment of the ChemR1 receptor gene to the p21.3-24 region of human chromosome 3, in close proximity with the functionally characterized CCR. Future work is required to identify the ligand(s) of this new chemokine receptor and to define its role in the recruitment of white blood cell populations.

Amino Acid Sequence↗
PubMed1996

High affinity thyroid hormone-binding protein in human kidney: kinetic characterization and identification by photoaffinity labeling.

The binding of thyroid hormones and its regulation of NADPH and NADP+ were studied in human kidney cytosol, and a 38-kDa polypeptide (p38) was identified by photoaffinity labeling of cytosol with underivatized [125I]T3, SDS-PAGE, and autoradiography. The cytosolic thyroid hormone binding and p38 photolabeling were strongly activated by NADPH (maximum at 10(-7) M), whereas other nucleotides were less effective or ineffective. NADP+ did not activate T3 binding and p38 photolabeling, provided it was protected from conversion to NADPH by the addition of an exogenous oxidizing enzymatic system (oxidized glutathione plus glutathione reductase). Furthermore, NADP+ inhibited NADPH activation (half-maximum inhibitory effect at approximately 2 x 10(-5)M), and oxidation of NADPH to NADP+ induced dissociation of bound T3. The equilibrium dissociation constant (Kd) of the NADPH-activated cytosolic T3-binding sites was 0.3 nM, similar to the Kd of the nuclear T3 receptors. The kidney contained 200 times more cytosolic NADPH-activated thyroid hormone-binding sites than nuclear T3 receptors. Nonradioactive iodothyronines competed with [125I]T3 for both NADPH-activated binding and p38 photolabeling, with the following order of decreasing affinity: D-isomer of T3 > T3 > T4 > triiodothyroacetic acid > 3'-isopropyl-3,5-diiodothyronine > rT3. NADPH-activated T3 binding and photolabeled p38 were also detected in human heart and liver cytosols, but not in pancreas, cultured fibroblast and erythrocyte cytosols, or plasma. Rat kidney cytosol contained a 35-kDa photolabeled polypeptide homolog to human p38. The native molecular mass of the human photolabeled protein was 50 kDa, whereas that of the rat protein was 60 kDa, as determined by nondenaturing polyacrylamide gel electrophoresis. Two-dimensional PAGE of photolabeled p38 indicated an isoelectric point of 5.3. These findings describe the molecular properties of a NADPH/NADP+-regulated thyroid hormone-binding protein not previously identified in human and rat kidney cytosol.

Affinity Labels↗
PubMed1996

Solubilization, reconstitution and molecular properties of the triiodothyronine transport protein from rat erythrocyte membranes.

Triiodothyronine (T3) transport through the mammalian erythrocyte membrane is mediated by a transport system related to the aromatic amino acid transport system T. The T3-binding component of this transport system could be photolabeled with [125I]T3 as a 52-kD protein, and subsequently solubilized with non-ionic detergents. Upon purification by ion-exchange chromatography, the photolabeled 52-kD protein solubilized with octylglucoside (OG) resolved into several peaks, suggesting charge heterogeneity of labeled proteins. The saturable [125I]T3 binding to rat erythrocyte membranes was completely inhibited by non-ionic detergents at concentrations about 20 times lower than those that solubilized membrane. Therefore, detergent-free proteoliposomes were generated from the detergent-soluble extracts by treatment with a polystyrene adsorbent. Proteoliposomes prepared from OG-soluble extract contained the highest specific activity of T3 binding. The Kd of the T3 binding sites (4.5 nmol/l) and the competitive inhibition constant of tryptophan (120 mumol/l) were similar to those for native membranes. The photolabeling of the 52-kD protein in these proteoliposomes was prevented by tryptophan and T4, but not by leucine or the D-isomer of T3, corresponding to the transport specificity of system T. The 52-kD protein solubilized with OG from native membranes was partially purified by ion-exchange chromatography. The 52-kD protein was detected by photoaffinity labeling in the purified fraction only after addition of erythrocyte membrane phospholipids to generate proteoliposomes. This indicates that the association of 52-kD protein with phospholipids is critical for T3 binding.

Affinity Labels↗
PubMed1994

[Clinical and evolutive aspects of cerebellar infarction].

This study included 125 cases of cerebellar infarction followed during an average period of 4.3 years. The diagnosis was made by CT or MRI. Infarctions localized to the territory of the superior cerebellar artery (SCA) and the territory of the posterior inferior cerebellar artery (PICA) occurred with the same frequency. Transient ischemic attacks preceded infarction in 26% of cases. Symptoms and signs were usual with sudden association of headache, dizziness, unsteadiness and vomiting. Vestibular signs were more important in infarctions of the PICA territory; cerebellar signs and dysarthria were more frequent in infarction of the SCA territory. A decreased level of consciousness developed in only 21% of cases. Surgical operation was required in 9 cases. Investigations have showed the large responsibility of cardiac embolisms and atherosclerosis. Short term outcome was more often favourable: 116 patients were alive at the end of the first month; 80% of survivors were independent one year later. At 5 years, 73% of patients were alive. After the acute period, mortality was mainly due to cerebro-vascular and cardiac events.

Actuarial Analysis↗
PubMed1994

Four axial structural and material test machine.

Structural tests of complex motion segments, such as those found in numerous joints in the body, require a flexible test bed capable of coordinated multiple axis control and a thorough understanding of the forces and moments. Past experience with such tests on the wrist, elbow, foot and spine joints pointed to the inadequacies of conventional test machines not designed for such purposes. Therefore, a PC-based four-axial benchtop test machine suited for more flexible, sophisticated, biomechanical testing has been developed and built. The test machine consists of a rigid aluminum frame incorporating three translational and one rotational axis driven by micro-stepping motors. The tester is controlled by an industry standard 486 PC including a motor indexer and analog-to-digital (A-D) board. The custom motion control software (not limited to four channels) is designed to accommodate both stepper and servo controllers in displacement or load control modes, or a feedback mode utilizing any number of A-D inputs to control axis velocity. Each axis can act independently, or dependently as a function of another axis. A six-component load cell was also incorporated for force and moment measurement. This new test machine has been found to be quite feasible and easy to operate in the analysis of joint constraint and laxity measurement.

Biomechanical Phenomena↗
PubMed1993

Identification by photoaffinity labeling of a membrane thyroid hormone-binding protein associated with the triiodothyronine transport system in rat erythrocytes.

Photoaffinity labeling with underivatized T3 was used to identify T3-binding proteins in the membrane of rat erythrocytes. UV irradiation of ghosts and peripheral protein-depleted membranes in the presence of [125I]T3 resulted in the covalent attachment of 125I to membrane proteins (analyzed by polyacrylamide gel electrophoresis and autoradiography). In the presence of the free radical scavenger dithiothreitol, 125I was selectively incorporated into a 45,000 mol wt band (p45) that was an integral membrane polypeptide. p45 photolabeling was half-inhibited by 14 nM unlabeled T3. This concentration is similar to the Km for T3 transport in rat erythrocytes and the Kd of the high affinity T3-binding sites under equilibrium binding conditions in the rat erythrocyte membrane. T4 and tryptophan also strongly inhibited p45 labeling, whereas the D-isomer of T3 was less efficient, and leucine had no effect. This corresponds to the specificity of the system T-related T3 transport system and T3-binding sites of rat erythrocytes. The SH-reagent N-ethylmaleimide prevented p45 labeling, unless T3 was present to protect the T3 transport activity and the high affinity T3-binding sites from inactivation. No saturable labeling of p45 or other polypeptides was detected in membranes prepared from human erythrocytes, which have very low T3 transport activity and no measurable high affinity T3-binding sites. p45 is not disulfide linked and is not a degradation product of higher mol wt polypeptides. Substrates and specific inhibitors of known erythrocyte membrane transporters did not alter p45 photolabeling, indicating that p45 is not functionally related to these transporters. We conclude that the photoaffinity-labeled T3-binding protein p45 has the properties expected of the T3-binding component of the T3 transport system in rat erythrocytes.

Affinity Labels↗
PubMed1993

[Quality of life and functional indices in osteoarthritis].

The main Indices of Quality of Life used in rheumatology and their aims and applications are surveyed. Their use in osteoarthritis implies a few issues that are addressed in a critical manner. Indices of Quality of Life are useful to measure deficiency resulting from osteoarthritis by comparison with other rheumatic diseases, as rheumatoid arthritis, connective tissue diseases, fibromyalgia... They are sensitive enough for apraising the domains improved by a radical treatment such as joint replacement. However, their scores are only slightly changing in most of the drug trials, in which the more simple functional indices seem demonstrative enough. Last but no least, they are notably time consuming for both the patient and the physician.

Activities of Daily Living↗
PubMed1993

[Unusual secondary coxarthrosis and posterior coxarthrosis].

Certain atypical forms of osteoarthritis of the hip are misleading: forms with very severe pain, forms with pain predominantly in the sitting position, forms with disproportionate pain. These atypical features can sometimes be explained by certain anatomical arrangements: superomedial narrowing over an aggressive double line, posterior osteoarthritis of the hip which can only be demonstrated on a false lateral view in the form of posteroinferior narrowing with its corollaries: anterosuperior diastasis and marked osteophytes of the posterior horn appearing to advanced underneath the femoral head on the lateral view. These atypical forms frequently only last several months or years. Posterior osteoarthritis of the hip has a less severe and slower course than the usual forms with superior narrowing.

Adolescent↗
PubMed1992

Triiodothyronine binding sites in the rat erythrocyte membrane: involvement in triiodothyronine transport and relation to the tryptophan transport System T.

The binding of L-triiodothyronine (T3) to rat erythrocyte membranes (ghosts and peripheral protein-depleted vesicles) was studied under equilibrium conditions. Ghosts contained high-affinity T3 binding sites whose dissociation constant (21 nM) was similar to the equilibrium-exchange Michaelis constant of T3 transport measured in ghosts. Each ghost contained about 8.10(3) high-affinity binding sites. The high-affinity T3 binding was stereospecific and was inhibited by L-tryptophan (Trp) but not by L-leucine. The iodothyronine and amino acid specificity of binding is therefore similar to that of System T, the erythrocyte T3/Trp transporter. These Trp-inhibitable high-affinity T3-binding sites were also present in peripheral protein-depleted membrane vesicles, indicating that they are integral part of the membrane. Ghosts prepared from human erythrocytes, which have very low System T transport activities, contained no detectable Trp-inhibitable high-affinity T3-binding sites. In rat erythrocyte ghosts, N-ethylmaleimide inactivated both the binding and the transport of T3. This inactivation was blocked by T3 and Trp with similar efficiencies. Phenylglyoxal, an arginine residue modifier, also inhibited both high-affinity T3 binding and System T transport activity. It is concluded that the Trp-inhibitable high-affinity T3-binding sites in the rat erythrocyte membrane are likely to be associated with System T.

Animals↗
PubMed1992

Thyroid hormone concentrative uptake in rat erythrocytes. Involvement of the tryptophan transport system T in countertransport of tri-iodothyronine and aromatic amino acids.

The kinetic properties of transport system T, which is specific for uptake of aromatic amino acids, were studied in rat erythrocytes in the presence of leucine in order to block the neutral amino acid transport system L. Since the triiodothyronine (T3) transport system and system T are closely related, the trans effect of T3 and tryptophan on [3H]tryptophan transport and the trans effects of aromatic amino acids on [125I]T3 transport were studied. Equilibrium-exchange, zero-trans and infinite-trans studies of [3H]tryptophan transport indicated that system T in rat erythrocytes is a simple carrier with exchanging properties resulting in trans-acceleration of influx and trans-inhibition of efflux when tryptophan was present at the trans side of the membrane. In erythrocytes preloaded with unlabelled tryptophan, countertransport resulted in a 7-fold accumulation of labelled substrate inside the cells. T3 on the trans side of the membrane inhibited both influx and efflux of tryptophan, with Ki values similar to the Km values of the T3 transport system. Extracellular tryptophan trans-inhibited [125I]T3 efflux in a manner similar to [3H]tryptophan efflux. Preloading erythrocytes with tryptophan resulted in trans-acceleration of T3 uptake and a transient 5-fold accumulation of free T3 into erythrocytes. Phenylalanine and tyrosine (but not the D-isomer of tryptophan or non-aromatic amino acids) also produced trans-acceleration for T3 uptake and T3 countertransport. These results are compatible with a kinetic model assuming a common simple carrier of T3 and tryptophan transport and point to a countertransport pathway driving the uphill uptake of T3 by hetero-exchange with intracellular aromatic amino acids.

Animals↗
PubMed1992

[The value of a clinical test for the evaluation of bladder-sphincter function in the management of urinary disorders of the elderly].

The authors report the value of a clinical test for the evaluation of vesico-sphincteric function in the demonstration of urinary disorders in the elderly. This simple, inexpensive test which can be performed at the patient's bedside, was performed in 175 elderly patients with a mean age of 81.2 years, mostly suffering from urinary incontinence (66.2%) and mostly (80%) derived from intermediate and long-term geriatric units. The mechanisms most often detected was detrusor instability (41% of patients). Cystomanometric data, obtained in 80 patients, were analysed and compared retrospectively with the data of the test: they demonstrated a good correlation in terms of evaluation of detrusor stability. As part of the overall management, this test constitutes a real diagnostic tool available to nursing staff, particularly in geriatric institutions not equipped with more specialised investigations.

Aged↗
PubMed1991

[Tendinitis of the hip region].

Tendinitis and bursitis are less common around the hip than around the shoulder. Nevertheless, they must be recognized to avoid unnecessary and costly diagnostic errors. Their various clinical forms are studied in detail. Tendino-bursitis of the gluteus medius muscle is the most frequent in its subacute form, but it is rare in its acute, pseudo-gouty form. Calcification of the reflected tendon of the rectus femoris muscle often closely resembles arthritis of the hip. Synovial cysts of the psoas bursa and rupture of the gluteus medius tendon are rare but must be known. Local injections of corticosteroids play an important part in the treatment of these diseases.

Hip Joint↗
PubMed1991

Acute complications of percutaneous transluminal coronary angioplasty for total occlusion.

The incidence of major complications after percutaneous coronary angioplasty (PTCA) of a totally occluded artery was assessed retrospectively. A total of 1649 PTCA procedures were analyzed. After exclusion of procedures for acute myocardial infarction or total occlusion that resulted from restenosis, 90 patients were selected. Forty-four patients (49%) had stable angina and 46 (51%) had unstable angina. The estimated duration of occlusion was 87 +/- 78 days in patients with stable angina, as compared with 10 +/- 8 days in patients with unstable angina (p less than 0.001). Abrupt vessel closure during PTCA occurred only in patients with unstable angina (0% versus 17%, p less than 0.05). The major complication rate was 2.5% in the stable angina group, and 20% in unstable angina group (p less than 0.01). This rate was also significantly higher than the complication rate of 8% observed in 442 procedures that were performed during the same period in patients with the unstable angina and nonocclusive stenosis (p less than 0.01). Patients with unstable angina who undergo PTCA of a totally occluded artery represent a subset of high risk for major complications.

Acute Disease↗