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Biomedical subjects

J Decker

Publications and source records attributed to J Decker.

At least 19 recordsLinked to original sources

Effects of chlorhexidine on proteolytic and glycosidic enzyme activities of dental plaque bacteria.

Chlorhexidine was tested for its ability to inhibit a wide range of glycosidic and proteolytic enzyme activities produced by Treponema denticola, Porphyromonas gingivalis, Bacteroides intermedius, Actinobacillus actinomycemcomitans, Capnocytophaga sputigena, Capnocytophaga gingivalis, Capnocytophaga orchracea, Capnocytophaga sp., Actinomyces viscosus, Streptococcus mitior, Streptococcus mutans, Streptococcus sobrinus, Streptococcus mitis, Streptococcus anginosus, Streptococcus oralis and Streptococcus sanguis. The enzymes produced by Capnocytophaga spp. were the most resistant to inhibition by chlorhexidine while the hydrolysis of proteolytic substrates by all the other species was markedly susceptible to inhibition with less than 0.125 mM chlorhexidine inhibiting enzyme activities by greater than or equal to 50%. Glycosidase activities, of all species, were generally more resistant to inhibition, especially neuraminidase activity. Chlorhexidine at less than 0.032 mM inhibited the degradation of bovine serum albumin by suspensions of dental plaque bacteria. These observations support an hypothesis that chlorhexidine exerts a bacteristatic effect in vivo, in part, by reducing the ability of dental plaque bacteria to degrade host-derived proteins and glycoproteins which normally provide essential nutrients for growth.

Acetylglucosaminidase

Determination of the molecular structure of the human free secretory component.

Here, we present the experimental data, leading to determination of the primary structure, the linkage of the carbohydrates and the arrangements of the disulfide bonds of the human free secretory component. Methods of protein chemistry were used. The protein can be divided into five homology regions and is a member of the immunoglobulin superfamily.

Amino Acid Sequence

Evidence that high mannose glycopeptides are able to functionally interact with recombinant tumor necrosis factor and recombinant interleukin 1.

Both recombinant tumor necrosis factor (rTNF) and recombinant interleukin 1 (rIL-1) are able to mediate vascular collapse and death in a previously described murine model, using galactosamine to enhance the toxicity of these cytokines. Unexpectedly, both acid-treated tumor necrosis factor (TNF) and a site-specifically mutagenized form of interleukin 1 (IL-1) (His-30----Arg-30), which fails to bind to the IL-1 receptor, retain full in vivo toxicity in this model of TNF- and IL-1-mediated shock. Previous studies have shown that rTNF and rIL-1 exhibit two functionally distinct binding regions. Both cytokines bind to their respective cell surface receptors and they also express lectin like binding specificity (Muchmore and Decker, J. Biol. Chem., 261: 13404-13407, 1986; Muchmore and Decker, J. Immunol., 138: 2541-2546, 1987) for defined oligosaccharides. The specificity of these two types of interactions is quite different. Cell surface receptors for IL-1 and TNF demonstrate essentially no cross-reactivity, whereas, in the case of carbohydrate binding, competition studies reveal an almost identical carbohydrate specificity for the structure Man5(6)GlcNAc2-Asn. Man5(6)GlcNAc2-Asn binding is either unaffected or actually enhanced by either acid treatment of rTNF or mutation at His-30 for rIL-1. Both deoxymannojirimycin and swainsonine, inhibitors of glycoprotein processing, raise intracellular levels of Man5-9GlcNAc2 and enhance the in vitro biological activity of both rTNF and rIL-1. Conversely, castanosperimine, a glucosidase I inhibitor which blocks the synthesis of mature high mannose structures, inhibits the biological activity of IL-1. These observations support the hypothesis that some effects of IL-1 and TNF may involve interaction with high mannose-substituted glycoproteins.

Animals

Evidence that specific high-mannose oligosaccharides can directly inhibit antigen-driven T-cell responses.

Uromodulin is an 85 Kd immunosuppressive glycoprotein originally isolated from human pregnancy urine. It is unique in that most of its biologic activity can be attributed to attached oligosaccharides. Purified immunomodulatory oligosaccharides from uromodulin have been structurally characterized using 1H-NMR spectroscopy and shown to be Man6-7GlcNAc2(M6,M7). Based on these observations, we isolated high-mannose N-type oligosaccharides and glycopeptides from ovalbumin, soybean agglutinin, and yeast mannan and show that these high-mannose compounds directly inhibit in vitro antigen-driven T-cell proliferation from millimolar to nanomolar concentrations. The most active compound was a core mannose oligosaccharide derived from yeast mannan, M9(y), which acts to block early events required for normal antigen processing/presentation. These data emphasize the potential functional role of carbohydrate structure in regulating the human immune response.

Antigens

SPARC: a Ca2+-binding extracellular protein associated with endothelial cell injury and proliferation.

SPARC (Secreted Protein that is Acidic and Rich in Cysteine) is a Ca2+-binding, stress-related protein released in vitro by both malignant and normal cells derived from all primordial germ layers. It is specifically elevated in endothelial cells as a result of "culture shock" (characterized by high levels of proliferation and migration) and exhibits density-dependent secretion. Exposure of bovine aortic endothelial cells to endotoxin results in a 70-100% increase in secreted protein, with a three-fold increase in SPARC. Immunofluorescence histochemistry on mouse tissues revealed (a) a preferential association of SPARC with highly proliferative cells (e.g., gut epithelia, mammary gland, and epidermis), (b) a cell surface or stromal location in thymus, lung, and salivary gland, (c) staining of epididymidal epithelium and testicular cells, and (d) an association with somites of 14 d mouse embryos. We envision SPARC as an extracellular modulator of Ca2+ and other cation-sensitive proteins/proteinases, that facilitates cellular proliferation in response to injury and to developmental signals.

Animals

Distribution of the calcium-binding protein SPARC in tissues of embryonic and adult mice.

SPARC (Secreted Protein that is Acidic and Rich in Cysteine), a Ca++-binding glycoprotein also known as osteonectin, is produced in significant amounts by injured or proliferating cells in vitro. To elucidate the possible function of SPARC in growth and remodeling, we examined its distribution in embryonic and adult murine tissues. Immunohistochemistry on adult mouse tissues revealed a preferential association of SPARC protein with epithelia exhibiting high rates of turnover (gut, skin, and glandular tissue). Fetal tissues containing high levels of SPARC included heart, thymus, lung, and gut. In the 14-18-day developing fetus, SPARC expression was particularly enhanced in areas undergoing chondrogenesis, osteogenesis, and somitogenesis, whereas 10-day embryos exhibited selective staining for this protein in Reichert's membrane, maternal sinuses, and trophoblastic giant cells. SPARC displayed a Ca++-dependent affinity for hydrophobic surfaces and was not incorporated into the extracellular matrix produced by cells in vitro. We propose that in some tissues SPARC associates with cell surfaces to facilitate proliferation during embryonic morphogenesis and normal cell turnover in the adult.

Animals

Motor organization of the spinal accessory nerve in the monkey.

The segmental and topographical organization of motoneurons of the spinal accessory nerve was studied in monkeys with horseradish peroxidase (HRP). The sternomastoid muscle is innervated primarily from the C1-C2 level of the cord and the motor column is medial in the ventral horn. The trapezius muscle, however, is innervated primarily from the C2-C3-C4 levels of the cord and the motor column lies in the ventrolateral region of the ventral horn. The data are discussed with regard to treatment of torticollis.

Animals

Pseudomonas dermatitis associated with a swimming pool.

One hundred forty-seven (66%) of 224 scouts and chaperons were interviewed after a weekend visit to a dude ranch in upstate New York. One hundred seventeen (80%) complained of papular rashes or eye and ear inflammation. Onset of illness occurred within 24 to 48 hours of arrival at the ranch. After controlling for participation in other available activities, only swimming was found to be associated with illness. Pseudomonas aeruginosa serotype 0 11 grew from a culture of pool water and from 17 cultures of skin, eye, and ear lesions in visitors to the ranch. Follow-up was obtained for 76 of the affected persons for whom initial information was available. Mean duration of illness was 14.5 days (range, one to 40+ days). The recurrence rate was 24%.

Adult

A receptor for IgA on human T lymphocytes.

Receptors for IgA antibody-antigen complexes were demonstrated on 2 to 18% (mean 6.7%) of human peripheral blood T cells. The proportion of cells bearing detectable IgA receptors was low in freshly prepared T cells and increased in number after 18 to 24 hr of culture similar to the time course of appearance of the Tmu receptor. These T receptors were shown to be distinctly different from Fc-IgM and Fc-IgG receptors on T cells by blocking studies with purified IgA, IgG, and IgM.

Animals

Morphologic comparison of piglets from first and second litters in chronic ethanol-consuming Sinclair(S-1) miniature swine.

Piglets (L-1) from 13 litters farrowed by 1-year-old, first litter alcohol-consuming dams were evaluated for altered morphology, A second group of piglets (L-2) farrowed by 6 second litter alcohol-consuming dams also was evaluated. Mean litter size and birth weight for L-1 piglets were 4.85 and 602 +/- 152 g; mean litter size and birth weight for L-2 piglets were 2.00 and 478 +/- 168 g. Fetal mortality rates for L-1 and L-2 piglets were 15 and 25%, respectively. Anomaly rates observed in fetal deaths were 11 and 100% for L-1 and L-2 piglets, respectively. L-1 anomalies were macrocephaly, microphthalmia, necrosis of bowel, nonexternalization of penile tissue, unascended kidney and unilateral renal hypodevelopment. L-2 anomalies were anencephaly, microcephaly, nonfusion of cranial sutures, macrocephaly, microphthalmia, nonfusion of mandibles, cleft palate, imperforate cloaca, sydactyly and polydactyly.

Abnormalities, Drug-Induced

Cross-modality transfer of spatial information.

First, second, and fourth grade boys and girls were tested on a spatial task requiring perception of the location of a group of three geometrical objects. The initial sensory input was either visual or tactual/kinaesthetic, and the choice stimuli, which were presented either simultaneously with the objects, or after the objects were removed (successively) were photographs of different configurations of the objects. There was no performance difference between th intramodal and cross-modal conditions, although older children performed better than younger ones, and performance was better under the simultaneous than successive conditions. It was concluded that in making complex visual spatial judgements, visual perceptual representations mediate performance under both tactual/kinaesthetic and visual sensory inputs.

Age Factors