Search PubMed⌕ Search

Biomedical subjects

M Lambert

Publications and source records attributed to M Lambert.

At least 343 records · Page 19Linked to original sources
PubMed1986

Effector mechanisms of peptides of the VIP family.

The present review is focused on the exocrine pancreas and liver where the only known effector mechanism of VIP is the activation of adenylate cyclase in plasma membranes. A two-state model of activation-deactivation of the enzyme visualizes the participation of VIP receptors and Ns, the guanyl nucleotide stimulatory protein of adenylate cyclase. In the rat pancreas, VIP and GRF receptors are indistinguishable and disulfide bridges influence their functional integrity. The antagonism of VIP and somatostatin perhaps requires, at the adenylate cyclase level, the contribution of Ni, the guanyl nucleotide inhibitory protein. The potentiation of VIP by various stimulants acting on Ca2+ movements may rely on later events, e.g., on a concerted activation of protein kinases. When comparing quantitatively peptide binding to receptors with adenylate cyclase activation, cyclic AMP levels and amylase secretion, a tool is at hand to tailor synthetic agonists and antagonists of VIP, with appropriate changes in the N-terminal moiety of the peptide (a good agonist allows efficient coupling of receptors to the adenylate cyclase system). Apart from stimulus-secretion coupling, VIP may influence protein synthesis in the rat pancreas, through the phosphorylation of ribosomal protein S6, and may alter the activity of the endoplasmic reticulum via the phosphorylation of Mr = 21 kDa and Mr = 25 kDa proteins. In rat liver membranes, high affinity VIP receptors are specifically labelled with 125I-helodermin and are coupled to adenylate cyclase (at variance with low affinity VIP receptors). These receptors are highly responsive to divalent cations and to guanyl nucleotides.

Adenylyl Cyclases↗
PubMed1986

Tritiated thymidine labelling in vitro of human cancer of the breast: counting error and sampling error.

Tritiated thymidine labelling indices (TLIs) were determined on a number of primary cancers of the human breast. Twenty-two slides were chosen which demonstrated a wide range of TLIs and each was counted twice to assess 'counting error'. TLIs derived from successive counts of the same slide showed a coefficient of variance greater than 25% in half of the slides, but a significant difference between the two (P less than 0.05) in only 2 of 22 pairs. When TLIs derived from paired specimens taken from different sites in each of 22 tumours were compared, there was found to be a significant difference (P less than 0.05) in 17 of 22 pairs. This is 'sampling error' and is clearly a major source of inaccuracy when TLIs are derived from single small samples of heterogeneous tumours such as cancers of the human breast.

Breast Neoplasms↗
PubMed1986

Estimation of compartmentation of lysine inside the cells of Yarrowia lipolytica.

We studied the compartmentation of lysine in vivo by the tracer method of Subramanian et al. (J. Bacteriol. 115 (1973) 284-290). To calculate the size of the different lysine pools and lysine fluxes inside the cell, a mathematical model was designed enabling quantitative estimation of these data from experimental measurements. This technique was applied to a lysine-accumulating strain, 15901.7, and to its low lysine pool derivatives, ply-1, ply-4 and ply-9, which were selected for their low polyphosphate pools. In the mother strain, 15901.7, it appeared that lysine was stored mainly in a non-cytoplasmic compartment. In the mutants, the efflux from this compartment was higher and accounted for the higher percentage of lysine in the cytoplasm of these strains. Simulation with calculated parameters fitted the experimental curves very well. This was good evidence for the pertinence of the model. The biological significance of these results are discussed.

Cytoplasm↗
PubMed1986

cDNA clones for liver cytochrome P-450s from individual aroclor-treated rats: constitutive expression of a new P-450 gene related to phenobarbital-inducible forms.

Differential hybridization and screening with cloned inserts was used to identify two families of cytochrome P-450 cDNA clones in libraries prepared from total liver poly(A)+RNA of individual Aroclor-treated rats. One family has cDNA inserts for the major phenobarbital-inducible P-450s, P-450b and P-450e. Two types of P-450e inserts were identified. In addition, irregular inserts were characterized from two clones (PB23 and PB24) of this group. The other family has cDNA inserts for the major 3-methylcholanthrene-inducible species, P-450c and P-450d. No coding sequence restriction site variants were detected among 26 P-450d and P-450c inserts analyzed. The restriction map of the irregular 2.2-kb PB23 insert has a P-450b-like portion, followed by a 3' extension that hybridizes to RNAs of 2.7 and 4.8 kb, which are also detectable with a classical P-450b probe. The PB23 insert and the 2.7- and 4.8-kb RNAs presumably represent 3' extensions of P-450b/P-450e mRNAs, polyadenylated at downstream sites. The 858-bp sequence of the PB24 insert encodes the carboxy-terminal portion of a P-450b/P-450e-like protein. There is approximately 20% divergence at the polypeptide level between the PB24 and P-450b/P-450e sequences; nevertheless, they share many essential features. A PB24-specific probe hybridizes to a 1.9-kb RNA species which is present in the liver of untreated rats and which is not appreciably induced by phenobarbital or Aroclor. The PB24 cDNA most likely represents a constitutive cytochrome P-450, related to phenobarbital-inducible forms.

Amino Acid Sequence↗
PubMed1986

Cardiovascular and blood gas responses to inhaled anaesthetics in normoxic and hypoxic dogs.

Changes in haemodynamics and blood gases were investigated before and after administration of 0.5, 1 and 1.5 MAC of halothane, enflurane and isoflurane in respectively 7, 7 and 9 dogs ventilated alternatively with a fraction of inspired O2 in N2 (FiO2) of 0.4 and with brief periods (10 min) of FiO2 of 0.1. Anaesthesia was induced with pentobarbital and the animals were paralysed with pancuronium. Acute hypoxic challenges with FiO2 of 0.1 consistently decreased arterial PO2 to 3.5-4.5 kPa and increased pulmonary vascular resistances by 60-100%. At identical inspired concentrations, as expressed in MAC units, all three inhaled anaesthetics induced a broadly comparable dose-related decrease in systemic blood pressures, due to a depression in cardiac performance as well as a reduction in systemic vascular resistances. Enflurane was the most potent myocardial depressor and isoflurane the most potent vasodilator, halothane being intermediate. Oxygen deprivation was associated with some enhancement of the cardiovascular depressant effects of the inhaled anaesthetics but, in spite of this, matching of O2 transport to tissue O2 demand appeared to be improved, probably in relation to a concomitant reduction in metabolic rate. Only isoflurane inhibited the hypoxic pulmonary pressor response, and this was associated with a slight deterioration in arterial oxygenation in both normoxic and hypoxic conditions.

Adaptation, Physiological↗
PubMed1986

[Prenatal diagnosis of hemophilia A by analysis of DNA].

Early ante-natal diagnosis of haemophilia A and the detection of female carriers is now possible in some cases by analysis of DNA. The diagnosis may be established with a 100 p. 100 reliability in subjects with large deletion by direct analysis, and in 40 p. 100 of haemophiliac families by linkage studies with the intra-genic polymorphism revealed by the restriction enzyme BcII. Intensive research indicates that this percentage will increase in the near future. In the meantime, indicative studies are possible in other families. They consist in studying extra-genic restriction polymorphism. Over 90 p. 100 of families with haemophilia A may benefit from these studies using the probes currently available. Recombination, although not yet described, remains possible, and therefore ante-natal diagnoses made by the extra-genic probe should be controlled by foetal blood sampling at the 20th week of pregnancy.

DNA↗
PubMed1986

Phase I study of triglycidylurazol given on a 5-day i.v. schedule.

Triglycidylurazol is a teroxirone derivative proposed for clinical trials on the basis of a broad spectrum of activity against murine tumors and a reduced potential for toxic manifestations at the injection site as compared to the parent compound. This phase I trial was designed to define the maximum tolerated dose of triglycidylurazol given by iv bolus on a 5-day schedule. Twenty-eight adult patients with a variety of solid tumors were entered. Their median performance status was 2 (range, 0-3), and most had received prior radiotherapy, chemotherapy, or both. A median of one course (range, one to four) was administered, for a total of 47 courses. Doses were escalated from 6 to 250 mg/m2/day. Leukopenia and thrombocytopenia were dose-related and -limiting, with a strong suggestion of increased myelosuppression with repeated courses. Nonhematologic toxic effects were generally mild to moderate. Nausea and vomiting were experienced by most patients. Local toxic effects consisting of venous discoloration, phlebitis, and/or sloughing were encountered in about one-half of the patients. Possible drug-related impairments in liver function were noted in three patients. Negligible alopecia and fatigue were also observed. Antitumor effect was detected in one patient with adenocarcinoma of unknown origin. A dose of 200 mg/m2/day for 5 consecutive days may be recommended for phase II trials.

Adult↗
PubMed1985

Solubilization from rat pancreatic plasma membranes of a cholecystokinin (CCK) agonist-receptor complex interacting with guanine nucleotide regulatory proteins coexisting in the same macromolecular system.

Using the non-denaturing detergent 3-[(3-cholamidopropyl)dimethylammonio]-2-hydroxy-1-propane sulfonate (Chaps), cholecystokinin (CCK) receptors were solubilized from rat pancreatic membranes as a reversible complex with the CCK 31-39 nonapeptide 125I-labelled by the Bolton and Hunter reagent. Bound ligand dissociation from this soluble complex was similar to that from the membranous receptors of origin and the marked increase in the rate of dissociation induced by GTP was preserved in the soluble state, indicating that the solubilized CCK receptors remained functionally coupled with the guanine nucleotide regulatory site modulating the affinity for CCK. In fact, two guanine nucleotide regulatory proteins, Ns and Ni, coexisted in the soluble complex as established by identifying the 42-kDa subunit of Ns and the 40-kDa subunit of Ni, after ADP-ribosylation by cholera toxin and Bordetella pertussis toxin, respectively.

Animals↗
PubMed1985

Amphiphilic cationic peptides mediate cell adhesion to plastic surfaces.

Four amphiphilic peptides, each with net charges of +2 or more at neutrality and molecular weights under 4 kilodaltons, were found to mediate the adhesion of normal rat kidney fibroblasts to polystyrene surfaces. Two of these peptides, a model for calcitonin (peptide 1, MCT) and melittin (peptide 2, MEL), form amphiphilic alpha-helical structures at aqueous/nonpolar interfaces. The other two, a luteinizing hormone-releasing hormone model (peptide 3, LHM) and a platelet factor model (peptide 4, MPF) form beta-strand structures in amphiphilic environments. Although it contains only 10 residues, LHM mediated adhesion to surfaces coated with solutions containing as little as 10 pmoles/ml of peptide. All four of these peptides were capable of forming monolayers at air-buffer interfaces with collapse pressures greater than 20 dynes/cm. None of these four peptides contains the tetrapeptide sequence Arg-Gly-Asp-Ser, which has been associated with fibronectin-mediated cell adhesion. Ten polypeptides that also lacked the sequence Arg-Gly-Asp-Ser but were nonamphiphilic and/or had net charges less than +2 at neutrality were all incapable of mediating cell adhesion (Pierschbacher and Ruoslahti, 1984). The morphologies of NRK cells spread on polystyrene coated with peptide LHM resemble the morphologies on fibronectin-coated surfaces, whereas cells spread on surfaces coated with MCT or MEL exhibit strikingly different morphologies. The adhesiveness of MCT, MEL, LHM, and MPF implies that many amphiphilic cationic peptides could prove useful as well defined adhesive substrata for cell culture and for studies of the mechanism of cell adhesion.

Amino Acid Sequence↗
PubMed1985

Pituitary apoplexy in an acromegalic patient during bromocriptine therapy. Case report.

The authors report a case of pituitary apoplexy that developed in a patient shortly after bromocriptine therapy was started for a growth hormone-secreting pituitary adenoma. The tumor was associated with visual impairment and ocular palsies, and was treated by transsphenoidal decompression. Although spontaneous tumor necrosis cannot be excluded, a causal role of bromocriptine treatment is suggested.

Adenoma↗