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Biomedical subjects

R Link

Publications and source records attributed to R Link.

At least 19 recordsLinked to original sources

Subtype-specific differences in the intracellular sorting of G protein-coupled receptors.

We have examined the subcellular distribution of three subtypes of adrenergic receptor by immunocytochemical localization of wild-type and epitope-tagged proteins expressed in Cos-7 and K293 cells. Two subtypes (beta 2 and M alpha 2-10H) are localized in the plasma membrane at steady state in untreated cells, while another subtype (M alpha 2-4H) is found both in the plasma membrane and in a population of intracellular vesicles. Within 15 min following the addition of adrenergic agonists, beta 2 and M alpha 2-10H receptors are differentially sorted; beta 2 receptors are selectively internalized to intracellular vesicles, which are distinct from those containing M alpha 2-4H receptors, while M alpha 2-10H receptors remain in the plasma membrane. Subtype-specific sorting suggests a new class of functional properties that may differentiate the signaling and regulation of homologous G protein-coupled receptors.

Amino Acid Sequence

Cloning of two mouse genes encoding alpha 2-adrenergic receptor subtypes and identification of a single amino acid in the mouse alpha 2-C10 homolog responsible for an interspecies variation in antagonist binding.

Molecular cloning and ligand binding studies have shown the alpha 2 class of adrenergic receptor (alpha 2-AR) to be a family of at least three related subtypes in humans. These studies have not, however, identified distinct subtype-specific functions for these receptors in vivo. It should be possible to extend the analysis of alpha 2-AR subtype function to the animal level through the use of experimental mammalian embryology in mice. To begin this process, we have isolated two mouse genomic clones encoding alpha 2-AR subtypes and expressed these genes in COS-7 cells for binding studies. Sequence homology and ligand binding data allow the assignment of one clone (M alpha 2-4H) as the mouse homolog of the human alpha 2-C4 subtype. The other clone (M alpha 2-10H) closely resembles the human alpha 2-C10 subtype in sequence but binds with significantly lower affinity to yohimbine and rauwolscine, members of a distinct class of bulky alpha 2-selective antagonists commonly used to evaluate alpha 2-AR function in vivo. To define the domain(s) responsible for this unusual binding property, we constructed a series of M alpha 2-10H/human alpha 2-C10 chimeric receptors. Analysis of these receptors identified a conservative Cys201 to Ser201 change in the fifth transmembrane domain of M alpha 2-10H as being responsible for the low affinity of the mouse receptor for yohimbine.

Adrenergic alpha-Antagonists

Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates.

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.

Animals

Comparison of tetracaine, adrenaline, and cocaine with cocaine alone for topical anesthesia.

A mixture of tetracaine, adrenaline, and cocaine (TAC) has been used extensively in the repair of small lacerations, especially in children. The purpose of this study was to determine whether cocaine alone would provide anesthesia equal to that of TAC, thus eliminating the risk of tetracaine toxicity and the theoretic risk of side effects from the combination of cocaine and adrenaline and simplifying preparation. One hundred thirty-nine patients were enrolled in a randomized, double-blind study comparing TAC with cocaine. Effectiveness was rated by the treating physician. Using the Wilcoxon rank-sum test, TAC was found to provide significantly better anesthesia than cocaine alone (P = .005). The percentage of patients having good anesthesia in the TAC-treated group was approximately 72%, which is equivalent to the efficacy found in other studies. Good anesthesia was obtained in 52% of the cocaine-treated group. No side effects or increased rates of infection were reported in either group.

Administration, Topical

Spinal empyema in Crohn's disease.

A 19-year-old man with a 1-year history of Crohn's disease of the ileum and rectosigmoid developed back and leg pain with neurological deficits. He proved to have an epidural and subdural spinal empyema originating from a rectal fistula. Drainage of the empyema, a diverting sigmoid colostomy, and appropriate antibiotics allowed full recovery of neurologic function and resolution of infection. We review the applicable literature.

Abscess

Dispase, a neutral protease from Bacillus polymyxa, is a powerful fibronectinase and type IV collagenase.

Dispase, a neutral protease isolated from culture filtrates of Bacillus polymyxa, has proven to be a rapid, effective, but gentle agent for separating intact epidermis from the dermis and intact epithelial sheets in culture from the substratum. In both cases it effects separation by cleaving the basement membrane zone region while preserving the viability of the epithelial cells. Because it is not known what or where in the basement membrane zone Dispase cleaves, we set up studies to define its substrate specificity. Using purified basement membrane components and sodium dodecyl sulfate-polyacrylamide gel electrophoresis we show that Dispase cleaves fibronectin and type IV collagen, but not laminin, type V collagen, serum albumin, or transferrin. The action of Dispase on collagen appears to be selective for type IV collagen in that several stable degradation products are formed, whereas the enzyme degrades type I collagen only minimally. In newborn human skin, as seen by electron microscopy, Dispase removes the lamina densa, rich in type IV collagen, but preserves the anchoring fibrils (structures known to contain type VII collagen) and the epidermal cells. Because its action is so selective, it suggests that Dispase can serve as a powerful tool for dissecting epithelial-mesenchymal interactions.

Basement Membrane

Phenylketonuria diet in adolescents--energy and nutrient intake--is it adequate?

The age at which phenylalanine (PA) restricted diet can be safely terminated in phenylketonuria (PKU) children has been the subject of discussion but a recent United States collaborative study has provided data showing that blood PA level should be kept below 10 mg/dl at least through adolescence. This presents nutritional problems in providing an adequate diet to meet the adolescent growth spurt in the absence of reliable information on the nutrient requirements of PKU adolescents. The problem is complicated by the emotional development of adolescence presenting compliance difficulties. The use of a computer programme to calculate nutrient intake and appropriate amino acid restricted diets for adolescents is described. It has been shown using the computer programme that an amino acid mixture specially adapted for use by adolescents is needed to provide sufficient vitamins, minerals and trace elements. Nutritional deficiency in adolescent PKU children may be a factor contributing to developmental abnormality.

Adolescent

Mortality study of persons exposed to dioxin in a trichlorophenol-process accident that occurred in the BASF AG on November 17, 1953.

Twenty-seven years after an accident which occurred in the BASF, Ludwigshafen plan in 1953, a mortality study of persons exposed to dioxin in an uncontrolled reaction during a trichlorophenol process was undertaken. The follow-up was 100% successful and involved 74 persons. Overall mortality (21 deaths) did not differ in this group from the rate expected in three external reference populations or from that observed in two internal comparison groups, where 18-20 deaths were observed. Of the 21 deceased persons, 7 had cancer, compared with 4.1 expected. In addition, two other cases of cancer (one bronchial carcinoma, and one carcinoma of the prostate) are still alive. Three deaths due to stomach cancer, at ages 64, 66, and 69 years, were found, compared with 0.6 expected from regional mortality data. One stomach cancer occurred among 148 individuals in the two comparison cohorts.

Accidents, Occupational

Histone phosphorylation in phorbol ester stimulated and beta-adrenergically stimulated mouse epidermis in vivo and characterization of an epidermal protein phosphorylation system.

Under certain physiological conditions a change in the phosphorylation of histones in mouse epidermis in vivo was observed. Thus a single local application of the tumor-promoting mitogen 12-O-tetradecanoylphorbol-13-acetate caused a long-lasting increase of histone H1 phosphorylation which paralleled stimulated cell proliferation. Injection of the antimitotic beta-adrenergic agonist isoproterenol led to a temporary decrease in the rate of phosphorylation of H1, H2A and H2B immediately after cyclic AMP accumulation. A complete protein phosphorylation system could be demonstrated in mouse epidermis homogenates. The following enzyme activities were partially purified and characterized: a cyclic AMP-dependent histone kinase; a 'casein kinase' and an 'unspecific' protein kinase; a histone-specific protein phosphatase; and two 'unspecific' phosphoprotein phosphatases. In addition, a stimulatory effect of cyclic GMP on histone phosphorylation was observed. The enzymes were found to be predominantly localized in the 105000 X g supernatant, but a small proportion of protein kinase and phosphatase activity could be regularly demonstrated in cell nuclei.

Animals

[Conservative treatment for acute otitis media (author's transl)].

The local treatment of acute otitis media consists of an early paracentesis or in the care of the external auditory canal when suppuration occurs. Causal treatment requires a restoration of the nose, the paranasal sinuses, and the nasopharynx to normal function. For general treatment, chemo- or antibiotic therapy is most prominent. Such is not always necessary, but if it is required, it must be given in high doeses until all cardinal symptoms have disappeared. An insufficient treatment leads to a pathomorphosis which can be observed as mucoid or secretory otitis media in 4--8 year old children.

Acute Disease

Measuring social and prevocational awareness in mildly retarded adolescents.

The social and Prevocational Information Battery contains nine subtests measuring social and prevocational awareness. It was developed and normed on secondary EMR pupils in Oregon. The battery is easy to administer, orally presented to eliminate reading ability as a determinant of performance, and relatively simple to score and interpret. Information concerning the standard error measurement and predictive validity inidicates that this battery may be used for pupil screeening, monitoring pupil progress, or for program evaluation.

Activities of Daily Living