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Biomedical subjects

M Lombard

Publications and source records attributed to M Lombard.

At least 19 recordsLinked to original sources
PubMed2004

Hereditary pancreatic endocrine tumours.

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.

Endocrine Gland Neoplasms↗
PubMed2004

Influence of opioid use on surgical and long-term outcome after resection for chronic pancreatitis.

BACKGROUND: The outcome of pancreatic resection for chronic pancreatitis in patients with preoperative opioid use is not well described. METHODS: During 1997 to 2003, 112 of 231 patients referred with chronic pancreatitis underwent pancreatic resection. The outcome of patients who had preoperative opioid use (N=46) was compared with those without (N=66). RESULTS: Patients who used opioids presented at a younger age and had a younger age of symptom onset, longer symptom duration, more hospitalizations, a higher frequency of diabetes mellitus, a higher pain score, and more restriction in daily activity (all P<.05). Twenty-one (46%) patients with opioid use had a total pancreatectomy compared with 9 (14%) without opioid use (P=.0002); the 21 patients also had a higher frequency of postoperative bleeding and early reoperation (8 vs 2, P<.02; 11 vs 3, P=.003, respectively). Mortality and overall morbidity was not significantly different between the 2 groups (4 vs 1, 27 vs 34, respectively). Pain scores improved postoperatively in both groups (P=.001) and was not significantly different between the groups from 12 months onward (median follow-up of 12 months, range, 3-60 months). Twenty percent of patients who used preoperative opioids however reverted to morphine use compared with 6% of patients who had not used opioids. CONCLUSIONS: Patients who used opioids had more advanced disease than patients without opioid use, accounting for part of the postoperative morbidity. Although long-term pain relief was comparable between the 2 groups, maintaining opioid withdrawal was more problematic in those with preoperative opioid use. Earlier referral for resection may be warranted in this group of patients.

Abdominal Pain↗
PubMed2003

Highly conserved chromosomes in an Asian squirrel (Menetes berdmorei, Rodentia: Sciuridae) as demonstrated by ZOO-FISH with human probes.

The chromosomes of Menetes berdmorei (Rodentia, Sciuridae, Sciurinae) were studied by ZOO-FISH using whole human chromosome probes. All homoeologies between M. berdmorei and human chromosomes were determined, except for two small chromosome segments. Twelve human chromosomes are conserved in a unique block of synteny; ten are split into two and one into three blocks. Thus, a small number of interchromosomal rearrangements, about twenty, separates human from this squirrel karyotype. Homoeologies between human and the presumed ancestral chromosomes of Sciurinae could also be deduced, as well as those with the presumed ancestral chromosomes of eutherian mammals. Sciurinae chromosomes appear to be much closer to those of non-rodent mammals than those of Muridae and Cricetidae species studied so far. Thus, they provide an interesting tool to link the rodent genome to those of other mammals.

Animals↗
PubMed2003

Reconstruction of the ancestral karyotype of eutherian mammals.

Applying the parsimony principle, i.e. that chromosomes identical in species belonging to different taxa were likely to be present in their common ancestor, the ancestral karyotype of eutherian mammals (about 100 million years old) was tentatively reconstructed. Comparing chromosome banding with all ZOO-FISH data from literature or studied by us, this reconstruction can be proposed with only limited uncertainties. This karyotype comprised 50 chromosomes of which 40-42 were acrocentrics. Ten ancestral pairs of chromosomes were homologous to a single human chromosome: 5, 6, 9, 11, 13, 17, 18, 20, X and Y (human nomenclature). Nine others were homologous to a part of a human chromosome: 1p + q (proximal), 1q, 2p + q (proximal), 2q, part of 7, 8q, 10p, 10q and 19p (human nomenclature). Finally, seven pairs of chromosomes, homologs to human chromosomes 3 + 21, 4 + 8p, part of 7 + 16p, part of 12 + part of 22 (twice), 14 + 15, 16q + 19q, formed syntenies disrupted in man.

Animals↗
PubMed2002

Endoscopic retrograde cholangiopancreatography should no longer be used as a diagnostic test: the case against.

Endoscopic retrograde cholangiopancreatography has been used successfully in diagnosis of pancreatico-biliary diseases. Over the past decade, there have been tremendous developments in radiological technologies which have led to the emergence of new and less invasive modalities like endoscopic ultrasound and spiral computed tomography and magnetic resonance cholangiopancreatography. Understandably, the usefulness of diagnostic endoscopic retrograde cholangiopancreatography is being questioned primarily because of its potential attendant complications. Therefore, this controversial question needs to be debated in the gastroenterology community. In this article, we compare the efficacy of newer diagnostic tools with existing "gold standard" modality--endoscopic retrograde cholangiopancreatography, and put forward our arguments in favour of a continuing role for endoscopic retrograde cholangiopancreatography as a diagnostic tool in certain circumstances.

Bile Duct Diseases↗
PubMed2002

Chromosomal characterization of Arvicanthis species (Rodentia, Murinae) from western and central Africa: implications for taxonomy.

A chromosome study of unstriped grass rats of the genus Arvicanthis (Rodentia, Murinae) in western and central Africa is presented. The observations extend the data available to 242 specimens from 59 localities. All individuals karyotyped belong to four karyotypic forms, or cytotypes, earlier described as ANI-1, ANI-2, ANI-3, and ANI-4 and are presumed to correspond to four distinct species. In order to provide diagnostic characters for these western and one central African Arvicanthis species, we standardized the chromosomal data available and developed a G- and C-banded chromosome nomenclature that allows easy species identification. Each form is characterized by a distinct geographical distribution, roughly following the biogeographical domains of western Africa, although their precise limits remain to be assessed. The sole area of sympatry detected is the region of the inner delta of the Niger River, where both ANI-1 and ANI-3 can be found. It is proposed that the three western African species ANI-1, ANI-3, and ANI-4 be renamed as A. niloticus, A. ansorgei, and A. rufinus, respectively.

Animals↗
PubMed2001

Pulse radiolysis studies on superoxide reductase from Treponema pallidum.

Superoxide reductases (SORs) are small metalloenzymes, which catalyze reduction of O2*- to H2O2. The reaction of the enzyme from Treponema pallidum with superoxide was studied by pulse radiolysis methods. The first step is an extremely fast bi-molecular reaction of the ferrous center with O2, with a rate constant of 6 x 10 (8) M(-1) s(-1). A first intermediate is formed which is converted to a second one with a slower rate constant of 4800 s(-1). This latter value is 10 times higher than the corresponding one previously reported in the case of SOR from Desulfoarculus baarsii. The reconstituted spectra for the two intermediates are consistent with formation of transient iron-peroxide species.

Catalysis↗
PubMed2001

Superoxide reductase from Desulfoarculus baarsii: reaction mechanism and role of glutamate 47 and lysine 48 in catalysis.

Superoxide reductase (SOR) is a small metalloenzyme that catalyzes reduction of O(2)(*)(-) to H(2)O(2) and thus provides an antioxidant mechanism against superoxide radicals. Its active site contains an unusual mononuclear ferrous center, which is very efficient during electron transfer to O(2)(*)(-) [Lombard, M., Fontecave, M., Touati, D., and Nivière, V. (2000) J. Biol. Chem. 275, 115-121]. The reaction of the enzyme from Desulfoarculus baarsii with superoxide was studied by pulse radiolysis methods. The first step is an extremely fast bimolecular reaction of superoxide reductase with superoxide, with a rate constant of (1.1 +/- 0.3) x 10(9) M(-1) s(-1). A first intermediate is formed which is converted to a second one at a much slower rate constant of 500 +/- 50 s(-1). Decay of the second intermediate occurs with a rate constant of 25 +/- 5 s(-1). These intermediates are suggested to be iron-superoxide and iron-peroxide species. Furthermore, the role of glutamate 47 and lysine 48, which are the closest charged residues to the vacant sixth iron coordination site, has been investigated by site-directed mutagenesis. Mutation of glutamate 47 into alanine has no effect on the rates of the reaction. On the contrary, mutation of lysine 48 into an isoleucine led to a 20-30-fold decrease of the rate constant of the bimolecular reaction, suggesting that lysine 48 plays an important role during guiding and binding of superoxide to the iron center II. In addition, we report that expression of the lysine 48 sor mutant gene hardly restored to a superoxide dismutase-deficient Escherichia coli mutant the ability to grow under aerobic conditions.

Animals↗
PubMed2001

Met-enkephalin is preferentially transported into the peripheral processes of primary afferent fibres in both control and HSV1-driven proenkephalin A overexpressing rats.

The demonstration of preproenkephalin A gene expression in rat dorsal root ganglia has raised the question of the physiological role of met-enkephalin-containing primary afferent fibres. Recently, we showed that systemic infection with a recombinant Herpes simplex virus encoding preproenkephalin A (HSVLatEnk1) yielded a marked increase in the density of met-enkephalin-like material synthesising neurons in rat dorsal root ganglia. This study further investigated the synthesis, transport and release of met-enkephalin-like material in the central and/or peripheral processes of primary afferent fibres in HSVLatEnk1-infected and control rats. In controls, dorsal root ganglia neurons containing met-enkephalin-like material were scarce and only a few positively labelled processes were seen at the peripheral output of the dorsal root ganglia. Met-enkephalin-like material accumulated at the proximal side of ligatured sciatic nerve, but not in ligatured L4-L5 dorsal roots. In HSVLatEnk1-infected rats with numerous somas and fibres stained for met-enkephalin-like material in dorsal root ganglia, met-enkephalin immunoreactive material largely accumulated at the proximal side of the ligatured sciatic nerve and few positively stained fibres were also observed in ligatured dorsal roots. Electrical stimulation of L4-L5 dorsal roots attached to a dorsal slice of the lumbar enlargement produced an overflow of met-enkephalin-like material which was approximately 70% higher in HSVLatEnk1-infected rats compared to controls. At the periphery, subcutaneous microdialysis showed higher basal levels of met-enkephalin-like material in the interstitial fluid of hindpaw plantar area in HSVLatEnk1-infected rats, and electrical stimulation of the ipsilateral sciatic nerve resulted in an approximately three-fold-higher overflow of this material than in control rats. These data demonstrated that met-enkephalin synthesised in dorsal root ganglion of both control and preproenkephalin A overexpressing rats is preferentially transported into the peripheral processes of primary afferent fibres where the peptide reaches a releasable compartment, thus providing a neuronal source of peripheral met-enkephalin.

Afferent Pathways↗
PubMed2001

Chromosome homologies between man and mountain zebra (Equus zebra hartmannae) and description of a new ancestral synteny involving sequences homologous to human chromosomes 4 and 8.

Using human chromosome painting probes, we looked for homologies between human and mountain zebra (Equus zebra hartmannae, Equidae, Perissodactyla) karyotypes. Except for two very short segments, all euchromatic regions were found to have a human homologous chromosome segment. Conserved syntenies previously described in various mammalian orders were detected. Each synteny corresponded to a chromosomal region homologous to two parts of human chromosomes: HSA3 and HSA21, HSA7 and HSA16, HSA12 and HSA22, and HSA16 and HSA19. Chromosomal segments homologous to a part of HSA11 and HSA19p are found syntenic in zebra, horse and donkey, suggesting that this group of synteny has been inherited from an Equidae or Perissodactyla common ancestor. A synteny of segments homologous to parts of HSA4 and HSA8 was observed in zebra and horse. It also exists in the rabbit (Lagomorpha) and several Carnivora species. A second group of taxa which does not have this region of synteny is composed of primates, Chiroptera and Insectivora, and possibly also Cetacea and Scandantia. Thus, the presence or absence of this region of synteny may separate two groups of eutherian mammals.

Animals↗
PubMed2000

Identification of the human Mnk2 gene (MKNK2) through protein interaction with estrogen receptor beta.

We have identified and characterized the human Mnk2 gene (HGMW-approved gene symbol MKNK2) through a yeast two-hybrid screen in which the Mnk2 protein interacted with the ligand-binding domain of estrogen receptor beta (ERbeta). Human Mnk2 is homologous to murine Mnk2 ( approximately 94% identical) and human Mnk1 (71% identical), both of which encode MAP kinase interacting kinases that are phosphorylated and activated by ERK1 and 2. This report presents a thorough genomic sequence analysis revealing that the human Mnk2 gene has two C-terminal splice variants, designated here as Mnk2a and Mnk2b. These two isoforms are identical over the first 385 amino acids of the coding sequence and differ only in the final exon which encodes an additional 80 residues for Mnk2a and 29 residues for Mnk2b. A more detailed biological analysis in yeast showed that the Mnk2 interaction was selective for ERbeta as opposed to ERalpha and that the interaction was specific to Mnk2b as opposed to Mnk2a or Mnk1. This pattern was reproduced in a mammalian two-hybrid system using a completely different set of fusion partners; and in both yeast and mammalian systems, the addition of estradiol decreased the interaction. While it remains unknown whether ERbeta is a substrate of Mnk2, the interaction of these two proteins is reminiscent of ERalpha and ribosomal S6 kinase (p90-RSK), another MAP kinase-regulated kinase homologous to Mnk2 that is known to phosphorylate ERalpha.

Amino Acid Sequence↗
PubMed2000

Superoxide reductase as a unique defense system against superoxide stress in the microaerophile Treponema pallidum.

Aerobic life requires the presence of antioxidant enzymes, such as superoxide dismutase, catalase, and peroxidase to eliminate deleterious oxygen derivatives. Treponema pallidum, a microaerophilic bacterium responsible for venereal syphilis, is an interesting organism because it lacks all of the above-mentioned enzymes, as deduced from its recently sequenced genome. In this paper, we describe a gene in T. pallidum with sequence homologies to a new class of antioxidant systems, named superoxide reductases, recently isolated from sulfate-reducing bacteria (Lombard, M., Fontecave, M., Touati, D., and Nivière, V. (2000) J. Biol. Chem. 275, 115-121). We report that (i) expression of the T. pallidum gene fully restored to a superoxide dismutase-deficient Escherichia coli mutant the ability to grow under aerobic conditions; (ii) the corresponding protein displays a strong superoxide reductase activity; and (iii) the T. pallidum protein contains only one mononuclear nonheme ferrous center, able to reduce superoxide selectively and efficiently, whereas previously characterized superoxide reductase from Desulfoarculus baarsii contains an additional rubredoxin-like ferric center. These results suggest that T. pallidum antioxidant defenses rely on a new class of superoxide reductase and raise the question of the importance of superoxide reductases in mechanisms for detoxifying superoxide radicals.

Amino Acid Sequence↗
PubMed2000

Reaction of the desulfoferrodoxin from Desulfoarculus baarsii with superoxide anion. Evidence for a superoxide reductase activity.

Desulfoferrodoxin is a small protein found in sulfate-reducing bacteria that contains two independent mononuclear iron centers, one ferric and one ferrous. Expression of desulfoferrodoxin from Desulfoarculus baarsii has been reported to functionally complement a superoxide dismutase deficient Escherichia coli strain. To elucidate by which mechanism desulfoferrodoxin could substitute for superoxide dismutase in E. coli, we have purified the recombinant protein and studied its reactivity toward O-(2). Desulfoferrodoxin exhibited only a weak superoxide dismutase activity (20 units mg(-1)) that could hardly account for its antioxidant properties. UV-visible and electron paramagnetic resonance spectroscopy studies revealed that the ferrous center of desulfoferrodoxin could specifically and efficiently reduce O-(2), with a rate constant of 6-7 x 10(8) M(-1) s(-1). In addition, we showed that membrane and cytoplasmic E. coli protein extracts, using NADH and NADPH as electron donors, could reduce the O-(2) oxidized form of desulfoferrodoxin. Taken together, these results strongly suggest that desulfoferrodoxin behaves as a superoxide reductase enzyme and thus provide new insights into the biological mechanisms designed for protection from oxidative stresses.

Amino Acid Sequence↗
PubMed2000

Common methylation characteristics of sex chromosomes in somatic and germ cells from mouse, lemur and human.

DNA methylation of sex chromosomes was analysed using anti-5-methylcytosine antibodies on metaphase chromosomes of somatic cells from three species: human, lemur and mouse. Germ cells were also studied in male mouse. In female cells (human and mouse), the late replicating X was always the less methylated chromosome. Compared with autosomes, the methylation of both X chromosomes was always lower in fibroblasts than in lymphocytes and the difference was always greater in mouse than in human. In human, mouse and lemur male cells, the labelling of the unique X chromosome was quite similar to that of the early replicating X from female cells. Except for the heterochromatic region of the human Y chromosome, strongly methylated, the overall methylation of the Y chromosome was low. In mouse testicular cells, a variety of DNA methylation patterns was observed according to the cell type and the state of differentiation. Finally, the only structures of sex chromosomes which remain methylated in all conditions correspond to their pseudoautosomal regions.

Animals↗
PubMed2000

Changes in thiamin, riboflavin, niacin, beta-carotene, vitamins, C, A, D and E status of French Elderly Subjects during the first year of institutionalization.

Vitamin status was assessed in 26 recently institutionalized elderly subjects by combining dietary and biochemical measurements of thiamin, riboflavin, niacin, beta-carotene, vitamins C, A, D and E at admission (P1), and 1.5 (P2), 3.0 (P3), 4.5 (P4), 6.0 (P5), 12 (P6) months later. At admission, except for vitamin A, mean vitamin intakes were lower than the 1992 French Recommended Dietary Allowance. Thiamin, vitamins C, A and E status seemed nearly satisfactory as less than one-fourth of the population sample had blood values lower than the cut-off point for thiamin (erythrocyte thiamin pyrophosphate < 0.17 mumol/l), vitamin A (serum retinol < 1.05 mumol/l), vitamin C (serum vitamin C < 11.3 mumol/l) and vitamin E (serum alpha-tocopherol < 9.3 mumol/l) or higher than the cut-off point for thiamin (erythrocyte transketolase activity coefficient > 1.19). Almost half of the subjects for riboflavin, and almost all non supplemented subjects for vitamin D were in risk of vitamin deficiency (46% had an erythrocyte glutathione reductase activity coefficient > 1.19 and 72% had a plasma 25(OH)D3 < 25 nmol/l). During the study, vitamins status remained unchanged for riboflavin, niacin, vitamins A, D and E, improved for vitamin C (P = 0.004) or impaired for thiamin (P = 0.008). Thus, institutionalization seemed to have no effect on riboflavin, niacin, vitamins A, D and E status and a slight effect on thiamin and vitamin C status.

Aged↗
PubMed2000

Phylogenetic origin of human chromosomes 7, 16, and 19 and their homologs in placental mammals.

The origin of human chromosomes (HSA) 7, 16, and 19 was studied by comparing data obtained from chromosome banding, chromosome painting, and gene mapping in species belonging to 11 orders of placental mammals (Eutherians). This allowed us to propose the reconstruction of their presumed ancestral forms. The HSA7 homologs were composed of two parts, the largest forming an acrocentric. The smallest formed one arm of a small submetacentric; the other arm was composed of sequences homologous to the short arm of HSA16 (HSA16p). The sequences homologous to the long arm of HSA16 (HSA16q) were associated with sequences homologous to the long arm of HSA19 (HSA19q) and formed another submetacentric. From their origin, these chromosomes underwent the following rearrangements to give rise to current human chromosomes: centromeric fission of the two submetacentrics in ancestors of all primates (approximately 80 million years ago); fusion of the HSA19p and HSA19q sequences, originating the current HSA19, in ancestors of all simians (approximately 55 million years ago); fusions of the HSA16p and HSA16q sequences, originating the current HSA16 and the two components of HSA7 before the separation of Cercopithecoids and Hominoids ( approximately 35 million years ago); and finally, pericentric and paracentric inversions of the homologs to HSA7 after the divergence of orangutan and gorilla, respectively. Thus, compared with HSA16 and HSA19, HSA7 is a fairly recent chromosome shared by man and chimpanzee only.

Animals↗