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Biomedical subjects

S Lebel

Publications and source records attributed to S Lebel.

At least 19 recordsLinked to original sources

Comparative morphology and paleobiology of Middle Pleistocene human remains from the Bau de l'Aubesier, Vaucluse, France.

The discovery of later Middle Pleistocene human remains from the Bau de l'Aubesier, France reinforces an evolutionary model of the gradual accumulation of Neandertal-derived facial and dental features during the Middle Pleistocene of the northwestern Old World. The pronounced maxillary incisor beveling of Aubesier 4 helps to extend the antiquity of nondietary use of the anterior dentition. The interproximal "toothpick" groove on the Aubesier 10 molar increases the sample for these lesions. The pathological loss of the mandibular dentition of Aubesier 11 indicates advanced antemortem masticatory impairment, at a level previously undocumented before the Late Pleistocene. These remains support a view of later Middle Pleistocene humans able to support debilitated individuals despite the considerable use of their bodies to accomplish routine activities.

Animals↗

Malabsorptive obesity surgery.

Biliopancreatic diversion is the only valuable surgical approach for changing intestinal absorption. It is efficient in producing appropriate permanent weight loss and has a considerable psychological advantage because it does not impose abnormal food restriction. It not only decreases caloric absorption, but it also directly improves insulin and lipid metabolism. The ideal technique for the construction of BPD is not yet established, but our current preference is for the duodenal switch type. BPD must be seen as a means to change an intolerable and untreatable disease to a tolerable and treatable one, with substantial improvement in quality of life.

Biliopancreatic Diversion↗

Biliopancreatic diversion (doudenal switch procedure).

The physiological principle underlying biliopancreatic diversion (BPD) is attractive. It decreases food absorption and particularly that of fat. It preserves normal eating habits and is compatible with a good quality of life. Because weight loss is not a function of an imposed aversion to eating, it is more appealing to patients. Data are accumulating showing that BPD can permanently cure morbid obesity in a majority of patients and is remarkably well tolerated. While long-term systemic side-effects from decreased absorption continue to raise concerns, available results have already shown that, within 20 years, metabolic disturbances are well tolerated while weight loss and quality of life are maintained. Vitamin and mineral replacement therapy and periodic monitoring are essential. The original procedure described by Scopinaro with subsequent modifications will be presented, focusing on the duodeno-ileal switch procedure.

Biliopancreatic Diversion↗

Accurate insertional inactivation of lacZalpha: construction of pTrueBlue and M13TrueBlue cloning vectors.

Color selection plasmid and phage vectors based on insertional inactivation of the lacZalpha gene fragment have been in wide use for nearly two decades. The originals (the pUC and M13mp series) and all subsequent derivatives of these vectors contain the same mechanism for insertional inactivation of lacZalpha placing the sites for gene interruption between the initiator ATG codon and codon 7, a region that encodes a functionally nonessential part of the lacZalpha-complementation peptide. Numerous observations found in the literature and made in our laboratory suggest that the color selection process in these vectors does not function reliably and that erroneous conclusions about the success of cloning experiments are frequently drawn. We have studied the efficiency of lacZalpha inactivation by performing insertions at different intervals along the entire length of the proximal 60-amino-acid (aa)-coding region of the lacZ gene (lacZalpha). Our results show that accurate and reliable inactivation of lacZalpha occurs only when insertions are made within the DNA region that encodes aa 11-36. Based on these results, novel color selection plasmid and phage vectors, pTrueBlue and M13TrueBlue, have been constructed. Application of these vectors for gap-free shotgun sequencing of genomic DNA is discussed.

Amino Acid Sequence↗

Conditional associative learning and the hippocampal system.

Rats with lesions of the fornix, the dorsal hippocampus, or a control operation were trained on a spatial-visual conditional associative learning task in which they had to learn to associate particular locations with specific visual stimuli. Animals with damage of the fornix were able to learn the task at a rate comparable to that of the control animals, but the performance of the hippocampal rats was significantly impaired in comparison with that of both the control and the fornix groups. In a second experiment, lesions to the fornix or the dorsal hippocampus significantly impaired performance on a spatial working memory task, the eight-arm radial maze. These findings suggest that the interaction between the hippocampus and subcortical structures via the fornix may be critical only for certain types of spatial learning and memory.

Animals↗

Biliopancreatic diversion with duodenal switch.

In 1990 Scopinaro's technique of biliopancreatic diversion with distal gastrectomy (DG) and gastroileostomy was modified. A sleeve gastrectomy with duodenal switch (DS) was used instead of the distal gastrectomy; and the length of the common channel was made 100 cm instead of 50 cm. A questionnaire and a prescription for blood work were sent to 252 patients who underwent DG a mean 8.3 years ago (range 6-13 years) and 465 patients who underwent DS 4.1 years ago (range 1.7-6.0 years). The questionnaire response rate was 93%, and laboratory work was completed for 65% of both groups. The mean weight loss after DG was 37 +/- 21 kg and after DS 46 +/- 20 kg. There were fewer side effects after DS: The number of daily stools was lower (p < 0.0002), as was the prevalence of diarrhea (p < 0.01), vomiting (p < 0.001), and bone pain (p < 0.001). Greater benefits related to several aspects of life were reported after DS than DG (p < 0.0001). The mean serum levels of ferritin, calcium, and vitamin A were higher (p < 0.001), and parathyroid hormone was lower. The yearly revision rate for excessive malabsorption was 1.7% per year after DG and 0.1% per year after DS. The two procedures were equally efficient for treating co-morbid conditions such as diabetes, hypertension, and hypercholesterolemia. Biliopancreatic diversion with sleeve gastrectomy/duodenal switch and a 100-cm common limb was shown to produce greater weight loss with fewer side effects.

Adolescent↗

Observations on the eruption of the permanent incisor teeth of farmed Javan rusa deer (Cervus timorensis russa) in New Caledonia.

The eruption of the permanent incisor teeth of 14 farmed Javan rusa deer (Cervus timorensis russa) of known birth date and their live weights were observed about every 2 weeks from 12 to 30 months of age. The permanent incisor pattern was 11, 14-17 months; 12, 18-23 months; 13, 20-26 months; and 14, 22-27 months. There was no significant relationship between body weight and timing of permanent incisor eruption.

Journal Article↗

Site-directed mutagenesis by complementary-strand synthesis using a closing oligonucleotide and double-stranded DNA templates.

An approach for generating structures capable of directing full-length complementary-strand synthesis for double-stranded plasmid DNA is described. The structures are formed following heat denaturation and cooling of linearized plasmid DNA molecules in the presence of what is referred to as a "closing" oligonucleotide. Consisting of a sequence complementary to the free ends of one of the two plasmid strands, the closing oligonucleotide functions as an agent for recircularization of a DNA strand and generation of a primer-circular template structure suitable for polymerase-dependent full-length complementary-strand synthesis and ligation into a covalently closed heteroduplex molecule. When combined with a mutagenic oligonucleotide and uracil-substituted DNA templates, this approach allows site-directed mutagenesis to be performed directly on double-stranded DNA with a mutant formation efficiency of about 50%, a level amenable to rapid screening by DNA sequencing.

Base Sequence↗

Development and inducibility of the hepatic and renal hippurate-synthesizing system in sparse-fur (spf) mutant mice with ornithine transcarbamylase deficiency.

The development of the hepatic and renal hippurate-synthesizing system, as represented by the overall reaction of the benzoyl CoA: glycine N-acyltransferase (EC 2.3.1.13) was studied in 0, 4, 8, 13, 17, 21-day and 8-week old sparse-fur (spf) mutant mice with X-linked ornithine transcarbamylase (OTC) deficiency. The enzyme system in mutant males (spf/Y) showed a retarded development in both liver and kidney cortex, which was statistically significant between 13 and 21 days of age, as compared to normal males (+/Y). Hippurate synthesis in preparations from adult (8-week old) spf/Y mice was not significantly different than the normal. Daily intraperitoneal injections of sodium benzoate in increasing concentrations (125-375 mg/kg), given between 17 and 21 days, did not cause any induction in spf/Y or +/Y mice. However, intraperitoneal sodium phenobarbital (80 mg/kg) increased the specific and total activities of the hepatic enzyme system in normal +/Y mice significantly. spf/Y tolerated a dose of 40 mg/kg only, which resulted in no significant increase of hepatic enzyme activity. The results indicate that barbiturates may induce the hippurate-synthesizing system, whereas benzoate treatment has no effect on changing its developmental profile.

Acyltransferases↗

Lamin A is not synthesized as a larger precursor polypeptide.

Isolation of rat liver nuclei in the presence of N-ethylmaleimide (NEM) led to the recovery in the final nuclear matrix of a higher molecular weight form of lamin A. The 2 kDa larger form was identified as lamin A by isoelectric point determination, recognition by an anti-lamin A and C monoclonal antibody and peptide mapping using V8 protease and N-chlorosuccinimide. The 2 kDa extension was tentatively localized to the carboxy-terminus of lamin A. Pulse-chase labeling and immunoprecipitation studies using baby hamster kidney cells showed that lysis of the cells in the presence of NEM allowed the recovery of a stable higher molecular weight form of lamin A. We conclude from these results that NEM prevented the degradation of the native form of lamin A previously thought to represent a higher molecular weight transient precursor form.

Animals↗

Lamins A, B and C share an epitope with the common domain of intermediate filament proteins.

Peripheral lamina were isolated from rat liver nuclei and probed with a monoclonal antibody reactive against a common domain of all intermediate filament (IF) proteins. The antibody reacted against lamins A and C as expected from their known sequence homology with IF proteins. Lamin B was also recognized by the antibody. These results indicate that lamin B, despite important biochemical differences vs lamins A and C, also shares sequence homology with IF proteins.

Animals↗

Lamins A and C appear during retinoic acid-induced differentiation of mouse embryonal carcinoma cells.

The lamin complement of nuclear matrix isolated from F9 embryonal carcinoma cells was studied during retinoic acid-induced differentiation in culture. Differentiation of the original cells into parietal endoderm-like cells was accompanied by the gradual appearance of lamins A and C while lamin B was present throughout all stages. Lamins were identified by their molecular masses, isoelectric points, recognition by a monoclonal antibody and a polyclonal antiserum, and by peptide mapping. The increase in the amounts of lamins A and C found in the matrix was due to de novo synthesis as no extranuclear pools of these lamins were detected in the undifferentiated cells. These results provide biochemical evidence that, as in amphibian embryogenesis, there are variations in nuclear lamina composition during mammalian development.

Animals↗

[Variability of enzyme activity and urinary orotic acid in ornithine transcarbamylase deficient spf/+ heterozygotic mice].

Urinary orotate excretion is used as a clinical parameter to distinguish female carriers of X-linked ornithine transcarbamylase deficiency. The value of this test has been considered doubtful due to a lack of knowledge about the true variability of hepatic enzyme activity and its effect on orotate synthesis. We have used a purebred population of spf/+ heterozygous females (n = 90), with an X-linked structural mutation of ornithine transcarbamylase, to study this variability in comparison with normal +/+ females (n = 19) and hemizygous spf/Y males (n = 20). Our results show that spf/+ heterozygotes have a mean hepatic enzyme activity equal to 64% of the normal group, as compared to 44-56% reported previously. They have a very wide variability (range 28-107 mumol/h/mg protein) which overlap the normal distribution curves of +/+ and spf/Y groups. Similar overlapping is shown in the distribution of urinary orotate excretion. The correlation studies indicate that the urinary orotate level as an index of hepatic enzyme deficiency is of value only in heterozygotes having an activity less than 50% of normal. This parameter cannot, therefore, be used to screen for all heterozygotes. However, it would still be valuable in distinguishing female-children at risk of developing hyperammonemic symptoms.

Animals↗

Lamin B from rat liver nuclei exists both as a lamina protein and as an intrinsic membrane protein.

Rat liver nuclear matrix structures were isolated while preserving the integrity of the nuclear envelope, i.e. in the absence of any detergent extraction. In order to determine the relationships between the nuclear membranes and peripheral lamina, nuclear matrix-envelope preparations were submitted to sodium carbonate extraction (0.1 M, pH 11.5), a solvent which solubilizes both peripheral membrane proteins and membrane-enclosed contents. One-dimensional and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of material insoluble in sodium carbonate confirmed that intrinsic membrane proteins were indeed retained in the membrane structures. Approximately 50 to 60% of the lamin B present in matrix-envelope preparations was found in these insoluble membranes while a smaller amount of lamin A and even less of lamin C resisted complete extraction. The identity of the lamins was confirmed by their migration on two-dimensional gels and by comparison of one-dimensional peptide maps. The same results were obtained using nuclear membranes prepared by a milder heparin procedure. The location of lamin B as an intrinsic membrane protein was also established by photoaffinity labeling with the membrane-penetrating reagent azidopyrene. A small but reproducible amount of labeling occurred as well on lamin A polypeptides. These results support the hypothesis that the peripheral lamina is attached to the nuclear envelope and anchored there via the presence of lamin B molecules within the bilayer of the inner nuclear membrane.

Animals↗