Characterization and developmental evolution of a high-affinity binding site for calcitonin gene-related peptide on chick skeletal muscle membrane.

Calcitonin gene-related peptide is a putative neurotransmitter of central and peripheral nervous systems which coexists with acetylcholine in motor nerve terminals and exerts multiple effects on skeletal muscle, suggesting a trophic role for this neuropeptide. Using radiolabeled calcitonin gene-related peptide as a probe in a specific binding assay, we have characterized calcitonin gene-related peptide binding sites on chick skeletal muscle membranes. Binding is time-dependent, saturable and reversible. Scatchard analyses revealed two classes of sites: high-affinity sites with a KD value of 62 pM, and low-affinity sites with a KD value of 3.3 nM. The maximal number of sites is, respectively, 22 and 155 fmol/mg protein for high- and low-affinity binding sites. Specific binding was not affected by the presence, in excess, of other neuropeptides such as salmon calcitonin or somatostatin or vasoactive intestinal polypeptide. Affinity of the binding site for calcitonin gene-related peptide was decreased in the presence of 5'-guanylyl-imidodiphosphate, suggesting a physiological coupling of calcitonin gene-related peptide receptor to a GTP binding protein. In a developmental study of chick muscle, we found the highest activity of calcitonin gene-related peptide binding sites in 11-14 day embryos, following a pattern of evolution similar to that of acetylcholine receptors (constant ratio of 12 acetylcholine receptors per calcitonin gene-related peptide binding site). However, both receptors appear differentially regulated: while the number of acetylcholine receptors increases 5-16-fold after denervation, calcitonin gene-related peptide binding sites slightly diminish in number. These results are discussed in terms of the physiological significance of calcitonin gene-related peptide binding sites on chick skeletal muscle membrane.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: results from a collaborative study.

PURPOSE: We expect that the mutation panel currently recommended for preconception/prenatal CF carrier screening will be modified as new information is learned regarding the phenotype associated with specific mutations and allele frequencies in various populations. One such example is the I148T mutation, originally described as a severe CF mutation. After implementation of CF population-based carrier screening, we learned that I148T exists as a complex allele with 3199del6 in patients with clinical CF, whereas asymptomatic compound heterozygotes for I148T and a second severe CF mutation were negative for 3199del6. METHODS: We performed reflex testing for 3199del6 on 663 unrelated specimens, including I148T heterozygotes, compound heterozygotes, and a homozygous individual. RESULTS: Less than 1% of I148T carriers were also positive for 3199del6. Excluding subjects tested because of a suspected or known CF diagnosis or positive family history, 0.6% of I148T-positive individuals were also positive for 3199del6. We identified 1 I148T homozygote and 6 unrelated compound heterozygous individuals with I148T and a second CF variant (2 of whom also carried 3199del6). In addition, one fetus with echogenic bowel and one infertile male were heterozygous for I148T (3199del6 negative). CONCLUSIONS: Reflex testing for 3199del6 should be considered whenever I148T is identified. Reflex testing is of particular importance for any symptomatic patient or whenever one member of a couple carries a deleterious CF mutation and the other member is an I148T heterozygote. Further population data are required to determine if I148T, in the absence of 3199del6, is associated with mild or atypical CF or male infertility.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

The superior laryngeal nerve loop and its surgical implications

Summary Based upon findings from 60 cadavers (120 sides), the incidence of superior laryngeal nerve loop, connecting the cervical sympathetic chain and the superior laryngeal nerve and its branches, the external and internal laryngeal nerve, was 98.3% (118 out of 120 sides). In most cases the loop connected the sympathetic chain and the external laryngeal nerve. The external laryngeal nerve was looped, and not linear as traditionally thought. The loop could be divided into three categories, V-shaped, U-shaped and mixed, and subdivided into 5 types and 17 subtypes according to morphological variation. The loop without exception innervated not only the cricothyroid muscle, but also the thyroid gland. The loop is one of the origins of the thyroid nerve. It seems that for thyroid surgery the loop, when lower in position, should be carefully separated from the superior thyroid vessels before the latter are ligated, in order to preserve a normal nerve supply to the muscle as well as to the part of the gland that remains after surgery.

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L'anse du nerf larynge supérieur, étude anatomique et applications chirurgicales

Résumé La fréquence d'une anse du nerf laryngé supérieur réalisant une anastomose entre la chaine sympathique cervicale et le nerf laryngé supérieur et/ou ses branches (rameau laryngé externe et ingerne), est de 98,3 % (118/120). Ce résultat s'appuie sur l'étude de 60 cadavres. Dans la plupart des cas, l'anastomose se fait entre la chaine sympathique cervicale et le rameau laryngé externe. Ce rameau laryngé externe a un trajet curviligne et non linéaire conformément aux données classiques. Il existe trois catégories d'anses : en "V", en "U" et mixte ; on peut également les subdiviser en 5 types et 17 sous-types en fonction des variations morphologiques. Cette anse innerve constamment non seulement le muscle cricothyroïdien mais aussi la glande thyroïde dont elle fournit une partie de l'innervation. Lors de la chirurgie thyroïdienne, si l'anse est en position basse, les nerfs doivent être soigneusement disséqués et séparés des vaisseaux thyroïdiens supérieurs avant ligature de ces derniers de façon à conserver l'innervation normale du muscle et de la partie restante de la glande.