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Biomedical subjects

F Martin

Publications and source records attributed to F Martin.

At least 145 records · Page 8Linked to original sources
PubMed1998

Cancer cell sensitization to fas-mediated apoptosis by sodium butyrate.

Cancer cells often resist Fas-mediated apoptosis even when the Fas receptor is expressed at the cell surface. We show here that human and rat colon cancer cells undergo massive apoptosis when they are exposed to soluble Fas ligand in the presence of sodium butyrate, an agent that induces by itself only a low rate of apoptosis. Sodium butyrate potentiates Fas-dependent apoptosis in seven out of eight colon cancer cell lines. Sodium butyrate does not increase Fas receptor cell surface expression and does not modify cell levels of Bcl-2, Bcl-xL, Bcl-xS and Bax. Sodium butyrate also induces tumor cell sensitization to the apoptotic effect of the combination of TNF-alpha and IFN-gamma, but it does not modify the level of the FADD/Mort1 adaptator molecule, at the connection between Fas- and TNF-dependent apoptosis pathways. Because the clinical toxicity of butyrate is low, its ability to enhance Fas-signal delivery in cancer cells could be of therapeutic interest.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Aetiology of childhood proptosis.

OBJECTIVE: To retrospectively analyse causes of childhood proptosis and their investigations and treatment. METHODOLOGY: The records of children under 15 years of age presenting with proptosis to The Children's Hospital, Camperdown, Sydney, were reviewed for the period 1983-93 inclusive. RESULTS: Fifty-seven cases of proptosis were found. In order of frequency the causes were; orbital cellulitis 22, thyroid eye disease 8, optic nerve +/- optic chiasm glioma 8, orbital rhabdomyosarcoma 7, metastatic neuroblastoma 4, orbital neurofibroma 3, orbital haemangioma 2, metastatic Ewing's sarcoma 2 and orbital dermoid cyst 1. Treatment depended on the cause (antibiotics, antithyroid drugs, chemotherapy, radiotherapy, surgery) and was multidisciplinary. CONCLUSIONS: The most common cause of proptosis in children presenting to The Children's Hospital, Camperdown, Sydney, was infective orbital cellulitis. The most useful initial investigation was an orbital computed tomography scan. Treatment depended on the cause of the proptosis and was multidisciplinary.

Adolescent↗
PubMed1998

Visual and brainstem auditory evoked potentials and maximal aerobic exercise: does the influence of exercise persist after body temperature recovery?

Transversal studies have shown a strong correlation between specific evoked potential (EP) values and specific physical activities, as well as between EP values and the amount of training. Prior to longitudinal studies investigating the effect of training in EPs, it is mandatory to determine whether a recent training session could interfere with regular EP recording. Exercise-induced hyperthermia is known to modify EP values. The purpose of the study was to determine whether an acute exercise can induce EP modification persisting after body temperature recovery. We measured two sets of visual evoked potentials (VEPs) and brainstem auditory evoked potentials (BAEPs) in 16 males (8 cyclists and 8 sedentary peers), one before and the other after a maximal cycloergometric graded exercise test. The second test was performed immediately after body temperature recovery. We chose to test cyclists, as their specific training corresponded to the exercise test we performed on a cycloergometer. The repeated measures before and after the exercise test showed no significant differences, neither in VEPs nor in BAEPs, for any subject of the study. Recording VEPs and BAEPs in cyclists, we observed no difference related to this particular sport training. This study showed that VEP and BAEP values were similar to those measured before a maximal exercise when body temperature returned to pre-exercise value. This original work demonstrated that VEP and BAEP recordings can be reliably performed after a recent training session, provided body temperature has returned to basal level.

Adolescent↗
PubMed1998

Engineering, characterization and phage display of hepatitis C virus NS3 protease and NS4A cofactor peptide as a single-chain protein.

The polyprotein encoded by hepatitis C virus (HCV) genomic RNA is processed into functional polypeptides by both host- and virus-encoded proteases. The HCV-encoded NS3 protease and its cofactor peptide NS4A form a non-covalent complex, which participates in processing the viral polyprotein. This proteolytic activity is believed to be essential for virus proliferation and thus the NS3 protease is a prime target for developing anti-HCV pharmacological agents. Recent X-ray crystallography structural studies have revealed the nature of this non-covalent complex between NS3 protease and the 'active' central segment of NS4A, providing the opportunity to design a single-chain polypeptide. To this end, the DNA sequence encoding for the NS4A peptide (residues 21-34) was genetically fused via a short linker, capable of making a beta-turn, to the N-terminus of the NS3 protease domain. This engineered single-chain NS3-protease (scNS3) is fully active with kinetic parameters virtually identical with those of the NS3/ NS4A non-covalent complex. Moreover, the scNS3 protease can be displayed on filamentous phage and affinity selected using an immobilized specific inhibitor. The scNS3 expressed as a soluble protein and in a phage-display format facilitates enzyme engineering for further structural studies and in vitro selection of potential drug-resistant mutants. These are important steps towards developing effective anti-protease compounds.

Amino Acid Sequence↗
PubMed1998

Eucalypt NADP-dependent isocitrate dehydrogenase. cDNA cloning and expression in ectomycorrhizae.

NADP-dependent isocitrate dehydrogenase (NADP-ICDH) activity is increased in roots of Eucalyptus globulus subsp. bicostata ex Maiden Kirkp. during colonization by the ectomycorrhizal fungus Pisolithus tinctorius Coker and Couch. To investigate the regulation of the enzyme expression, a cDNA (EgIcdh) encoding the NADP-ICDH was isolated from a cDNA library of E. globulus-P. tinctorius ectomycorrhizae. The putative polypeptide sequence of EgIcdh showed a high amino acid similarity with plant NADP-ICDHs. Because the deduced EgICDH protein lacks an amino-terminal targeting sequence and shows highest similarity to plant cytosolic ICDHs, it probably represents a cytoplasmic isoform. RNA analysis showed that the steady-state level of EgIcdh transcripts was enhanced nearly 2-fold in ectomycorrhizal roots compared with nonmycorrhizal roots. Increased accumulation of NADP-ICDH transcripts occurred as early as 2 d after contact and likely led to the observed increased enzyme activity. Indirect immunofluorescence microscopy indicated that NADP-ICDH was preferentially accumulated in the epidermis and stele parenchyma of nonmycorrhizal and ectomycorrhizal lateral roots. The putative role of cytosolic NADP-ICDH in ectomycorrhizae is discussed.

Amino Acid Sequence↗
PubMed1998

Carbohydrate and amino acid metabolism in the eucalyptus globulus-pisolithus tinctorius ectomycorrhiza during glucose utilization

The metabolism of [1-13C]glucose in Pisolithus tinctorius cv Coker & Couch, in uninoculated seedlings of Eucalyptus globulus bicostata ex Maiden cv Kirkp., and in the E. globulus-P. tinctorius ectomycorrhiza was studied using nuclear magnetic resonance spectroscopy. In roots of uninoculated seedlings, the 13C label was mainly incorporated into sucrose and glutamine. The ratio (13C3 + 13C2)/13C4 of glutamine was approximately 1.0 during the time-course experiment, indicating equivalent contributions of phosphoenolpyruvate carboxylase and pyruvate dehydrogenase to the production of alpha-ketoglutarate used for synthesis of this amino acid. In free-living P. tinctorius, most of the 13C label was incorporated into mannitol, trehalose, glutamine, and alanine, whereas arabitol, erythritol, and glutamate were weakly labeled. Amino acid biosynthesis was an important sink of assimilated 13C (43%), and anaplerotic CO2 fixation contributed 42% of the C flux entering the Krebs cycle. In ectomycorrhizae, sucrose accumulation was decreased in the colonized roots compared with uninoculated control plants, whereas 13C incorporation into arabitol and erythritol was nearly 4-fold higher in the symbiotic mycelium than in the free-living fungus. It appears that fungal utilization of glucose in the symbiotic state is altered and oriented toward the synthesis of short-chain polyols.

Journal Article↗
PubMed1998

Disseminating multimedia protocols over Internet for emergency and catastrophe management.

Over the last years we have developed various computing methods to assist specialized personnel on various aspects of catastrophe and emergency management. New models can address tasks such as patient triage; stabilization, resource coordination and hospital alertness and techniques based on information technologies. In this paper we present various tools (written on Java and C+2) that we created to store, represent, and disseminate practice guidelines and protocols over the World Wide Web. Guidelines and protocols are stored using a standard database program (e.g., Microsoft Access), and represented in a flowchart format linked to multimedia information such as text, pictures, sound, video or external sources of data. Using our JAVA tool, protocols can be disseminated over the Web and viewed with any browser with JAVA compliance. We have implemented 15 emergency protocols that we developed in collaboration with specialized military personnel from the Ministry of Defense, Spain. Users can access remotely those electronic protocols comparing their procedures and methods. Our goal is to enhance agreement and consensus among remote medical centers regarding emergency and catastrophe management, establishing discussions over the network. Our tools have also a potential for training medical and paramedical personnel for emergency situations.

Clinical Protocols↗
PubMed1998

Cytosolic calcium oscillations and insulin release in pancreatic islets of Langerhans.

Stimulation of insulin release by glucose and other nutrients has been attributed to a rise of cytoplasmic Ca2+([Ca2+]i). In intact pancreatic islets, this rise is organized in oscillations. Two types of [Ca2+]i oscillations are mainly detected. Fast oscillations (frequency of approximately equal to 3 min-1) are consistently observed, and their duration depends on glucose concentration. They are due to a bursting of electrical activity and occur synchronously throughout the islet. Slow oscillations (frequency of 0.2 min-1) also appear in response to other nutrient secretagogues (ketoisocaproate, leucine, isoleucine). They most probably constitute the physiological oscillatory pattern because islets perifused with a solution containing a mixture of amino acids and glucose at concentrations found in the plasma of fed animals showed the same oscillatory pattern. Slow [Ca2+]i oscillations may constitute the framework for pulsatile insulin release observed in vivo.

Amino Acids↗
PubMed1998

[The Fas/Fas-ligand system: implications in the antitumor immune response and in the activity of cytotoxic agents].

Interaction of Fas-ligand (Fas-L) with the extracytoplasmic domain of the Fas receptor can induce Fas trimerization and activation of the apoptotic cell death process. Several molecular pathways that lead to apoptosis and some of their regulatory mechanisms have been identified. Fas-related membrane receptors that contain a death domain in their intracytoplasmic domain have been identified. They constitute a death receptor family (DR1 to DR5) whose first member is the TNFR1 receptor for TNF alpha. The Fas/Fas-L system plays a role in the cytotoxic activity of immune cells and the regulation of immune response amplitude. This system could be involved in the immune response to tumor cells and the cytotoxic activity of drugs and radiations. The expression of Fas-L on the plasma membrane of numerous tumor cells allow them, in vitro, to kill Fas-expressing immune cells. This observations has suggested that tumor cells used Fas-L to induce a specific immune tolerance. However, in vivo, Fas-L expression rather induces tumor cell rejection. The quantity of Fas-L expressed on tumor cells could determine whether tumor cells are tolerated or rejected. Cytotoxic drugs and radiations modulate Fas and Fas-L expression on tumor cells. The role of Fas/Fas-L interactions in the cytotoxicity of these agents remains poorly defined. It has been clearly shown, however, that low doses of cytotoxic drugs increase Fas expression on tumor cells, thereby improving their elimination by immune cells. Drug-induced modulation of Fas expression could provide new therapeutic strategies combining chemotherapy with immunotherapy.

Animals↗
PubMed1998

[Amelioration of perioperative somatosensory evoked potentials in the surgery of injuries of the spine].

Somatosensory evoked potentials were performed in 38 patients with traumatic spine pre, per and postoperatively. In 3 cases, the S.E.Ps altered before surgery, were improved after decompression and reduction. This S.E.Ps improvement was associated to clinical improvement. Even though this study was carried out on few cases, it shows prognosis and diagnosis value of intraoperative S.E.Ps in traumatic spine surgery.

Adult↗
PubMed1997

Mirror image alternative interaction patterns of the same tRNA with either class I arginyl-tRNA synthetase or class II aspartyl-tRNA synthetase.

Gene cloning, overproduction and an efficient purification protocol of yeast arginyl-tRNA synthetase (ArgRS) as well as the interaction patterns of this protein with cognate tRNAArgand non-cognate tRNAAspare described. This work was motivated by the fact that the in vitro transcript of tRNAAspis of dual aminoacylation specificity and is not only aspartylated but also efficiently arginylated. The crystal structure of the complex between class II aspartyl-tRNA synthetase (AspRS) and tRNAAsp, as well as early biochemical data, have shown that tRNAAspis recognized by its variable region side. Here we show by footprinting with enzymatic and chemical probes that transcribed tRNAAspis contacted by class I ArgRS along the opposite D arm side, as is homologous tRNAArg, but with idiosyncratic interaction patterns. Besides protection, footprints also show enhanced accessibility of the tRNAs to the structural probes, indicative of conformational changes in the complexed tRNAs. These different patterns are interpreted in relation to the alternative arginine identity sets found in the anticodon loops of tRNAArgand tRNAAsp. The mirror image alternative interaction patterns of unmodified tRNAAspwith either class I ArgRS or class II AspRS, accounting for the dual identity of this tRNA, are discussed in relation to the class defining features of the synthetases. This study indicates that complex formation between unmodified tRNAAspand either ArgRS and AspRS is solely governed by the proteins.

Anticodon↗
PubMed1997

The Tim core complex defines the number of mitochondrial translocation contact sites and can hold arrested preproteins in the absence of matrix Hsp70-Tim44.

Preprotein import into mitochondria is mediated by translocases located in the outer and inner membranes (Tom and Tim) and a matrix Hsp70-Tim44 driving system. By blue native electrophoresis, we identify an approximately 90K complex with assembled Tim23 and Tim17 as the core of the inner membrane import site for presequence-containing preproteins. Preproteins spanning the two membranes link virtually all Tim core complexes with one in four Tom complexes in a stable 600K supercomplex. Neither mtHsp70 nor Tim44 are present in stoichiometric amounts in the 600K complex. Preproteins in transit stabilize the Tim core complex, preventing an exchange of subunits. Our studies define a central role for the Tim core complexes in mitochondrial protein import; they are not passive diffusion channels, but can stably interact with preproteins and determine the number of translocation contact sites. We propose the hypothesis that mtHsp70 functions in protein import not only by direct interaction with preproteins, but also by exerting a regulatory effect on the Tim channel.

Amino Acid Sequence↗
PubMed1997

Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats.

Tumors are tolerated by the immune system notwithstanding the expression of tumor-associated antigens. PROb tumor cells, derived from a rat colon carcinoma, are rejected by tumor-immune hosts but give rise to progressive tumors in naive hosts. Paradoxically, these tumors are heavily infiltrated by dendritic cells that express MHC class II and ICAM-1. These tumor-infiltrating dendritic cells (TiDCs) could be expected to process and present to T cells the antigens released by the adjacent tumor cells. Indeed, we report here that TiDCs, compared with splenic dendritic cells, are poor stimulators of primary allogeneic T-cell proliferation and cytokine [interleukin-2 (IL-2) and interferon-gamma] production. Most of them (89-97%) do not express B7, an essential co-stimulatory signal for T cells, even after a culture period allowing B7 up-regulation on epidermal Langerhans cells. GM-CSF in association with tumor necrosis factor-alpha or IL-4, or cell-associated CD40-ligand, all known to be potent stimulators of B7 expression on other dendritic cells, did not restore B7 expression by TiDCs. After a first exposure to TiDCs, allogeneic T-cell response to a second challenge to splenic dendritic cells was decreased. The failure of most dendritic cells infiltrating PROb tumors to express B7, even after stimulation, may contribute to their poor capacity to stimulate T cells and could play a role in the immune tolerance allowing tumor growth.

Adenocarcinoma↗