Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-gamma (IFN-gamma) suppresses the synthesis of collagen by fibroblasts in vitro and the synthesis of collagen in vivo in animal models. Therefore, recombinant human IFN-gamma was examined for its ability to clinically modify keloids. Subjects were treated by injection of either 0.01 or 0.1 mg of recombinant human IFN-gamma into one lesional site and diluent alone into another lesional site three times per week for 3 weeks. Keloids were measured and photographed before beginning therapy and weekly thereafter. Three days after the final injection, biopsies were performed on treated and control sites. Six of eight subjects who finished the course of treatment demonstrated reduction in size at the treated site with an average reduction in height of 30.4% vs 1.1% for control sites. Lesions treated with recombinant human IFN-gamma demonstrated alterations in both the epidermis and dermis. The epidermis showed thinning of the suprapapillary plates, compact hyperkeratosis, focal or diffuse parakeratosis, exocytosis of lymphocytes, and an increased quantity of mucin. The dermis contained a diminished quantity of thickened collagen bundles and active fibroblasts and an increased number of inflammatory cells and quantity of mucin. These results suggest the feasibility of using IFN-gamma in the treatment of abnormal fibrosis. Dose-ranging studies are required to establish whether IFN-gamma can fulfill a true clinical need in the treatment of keloidal scarring.
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PMID:A controlled trial of intralesional recombinant interferon-gamma in the treatment of keloidal scarring. Clinical and histologic findings. 212 Nov 4

Retinoids profoundly influence epidermal differentiation, but neither the nature of their antikeratinizing activity nor their mechanism of action is known. In this study, we have correlated morphologic and histochemical findings with an assessment of stratum cohesion and water barrier integrity in adult hairless mice treated with either 13-cis-retinoic acid or the aromatic retinoid, RO 10-9359. Both the synthetic retinoids produced dose-dependent alterations in transepidermal water loss, which were about 5 to 10 times greater in RO 10-9359-treated animals. In contrast to essential fatty acid deficiency, where diminished intercellular lamellar lipids may account for defective barrier function, these lipid-rich structures were intact in retinoid-treated tissues. Instead, retinoids produced both epidermal and stratum corneum loosening, manifested both by the ready production of intraepidermal friction blisters and by ease of removal of cornified cells by tape stripping. Dyshesion correlated with loss of desmosomes and intra- and intercellular accumulation of amorphous material in the upper epidermis. Since these deposits lacked the tinctorial properties of mucin, dyshesion could not be ascribed to the development of mucous metaplasia. Finally, dyshesion could not be attributed to either gain or loss of membrane sugars demonstrated with rhodamine-conjugated lectins, since these changed only late in the course of retinoid treatment. We conclude that the antikeratinizing basis for retinoid activity comprises: (1) dose-dependent alterations in transepidermal water loss and (2) epidermal and stratum corneum loosening, which may, in turn, lead to loss of epidermal cohesion and abnormal barrier function. Neither mucous metaplasia nor stratum corneum thinning appear to play a major role.
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PMID:Retinoid effects on epidermal structure, differentiation, and permeability. 693 40

The mucin secretagogue 15(S)-HETE was found to stimulate glycoprotein secretion in human ocular tissue at submicromolar concentrations in the present studies. Therefore, the ability of topically applied 15(S)-HETE to preserve corneal integrity was investigated in a rabbit model of desiccation-induced corneal defect. Desiccation-induced corneal injury was elicited in anesthetized rabbits by maintaining one eye open with a speculum. Corneal staining and corneal thickness changes were determined immediately following desiccation. 15(S)-HETE dose-dependently reduced corneal damage (ED50 = 120 nM) during a two-hour desiccation. Corneal staining was unchanged relative to control using a 1 microM dose of 15(S)-HETE. Through four hours of desiccation, 15(S)-HETE (500 nM) decreased corneal staining by 71% and completely prevented corneal thinning. 15(S)-HETE (1 microM) was significantly more efficacious than an artificial tear product over the 4-hour desiccation period. There was no evidence of tachyphylaxis following repeated topical ocular dosing of 15(S)-HETE. These studies demonstrate that 15(S)-HETE stimulates ocular mucin secretion in vitro and effectively protects the cornea in a rabbit model of desiccation-induced injury. The results suggest that the ocular mucin secretagogue 15(S)-HETE may have therapeutic utility in dry eye patients, alleviating corneal injury and restoring corneal integrity.
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PMID:Corneal protection by the ocular mucin secretagogue 15(S)-HETE in a rabbit model of desiccation-induced corneal defect. 1222 65

The modified method of the microbiological study of parietal mucin has been developed. The proposed method makes it possible to evaluate the parietal microflora of the intestine. The advantages of using physiological saline and Hanks' solution as medium ensuring the storage and self-thinning of mucin have been proved. The optimum time of making the microbiological study of intestinal mucin has also been determined.
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PMID:[Parital microflora of human intestine]. 1263 Mar 56

Human tear viscosity is poorly understood. Tears need to remain on the ocular surface for lubrication without causing damage to the surface epithelia due to drag when blinking. Whole tears are shear-thinning (non-Newtonian), which cannot be explained by the amount of mucin present, nor by individual proteins. Whole tears minus lipids become Newtonian. Though no free lipids had previously been found in collected tears, tear lipocalin (TL), a major tear protein, is known to bind lipids. In this study, we aimed to confirm whether there are any free lipids in collected tears, and to clarify the combined contribution of tear proteins to viscosity, including experiments on recombinant TL, both without (apo-TL) and with (holo-TL) bound lipid. We also investigated possible oligomer formation by holo- and apo-TL as a mechanism for viscosity using SDS-PAGE and analytical ultracentrifugation (AU). For comparison, we have included results for beta-lactoglobulin, a well-characterised lipocalin protein. No free lipids were detected in whole tears. Rheology showed that any protein combination that included lysozyme or lactoferrin was shear-thinning, as was apo-TL, though holo-TL was Newtonian (linear). Results from SDS-PAGE and AU showed apo-TL to be entirely monomeric, but holo-TL showed some dimerization. Both apo- and holo-beta-lactoglobulin exhibited a monomer-dimer equilibrium. We conclude that hetero-protein interactions, possibly electrostatic, involving lipid-binding-induced structural changes to TL, significantly contribute to the viscosity of human tears.
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PMID:Human tear viscosity: an interactive role for proteins and lipids. 1623 63

Mucus accumulation in the lower airways is a key feature of cystic fibrosis (CF) lung disease. The major component of mucus in CF is not mucin derived from mucus producing cells but rather pus that includes viscous material such as polymerized DNA derived from degraded neutrophils. This has important implications for mucolytic therapy aiming to improve mucus clearance from the airways, since degradation of mucin may not be a suitable treatment strategy. In addition, thinning of secretions may not always be beneficial, since it may negatively affect certain aspects of mucus transport such as cough clearance. While inhaled N-acetylcysteine has been used as a mucolytic drug in CF for decades, there is little evidence that it has any beneficial effect. Dornase alfa has been shown to reduce pulmonary exacerbations and improve lung function and is currently the only mucolytic agent with proven efficacy in CF. Newer agents targeting other components of CF mucus, such as filamentous actin, are currently in development. Ultimately, drugs that are mucokinetic, which preserve viscoelasticity, rather than mucolytic may prove to be beneficial for CF lung disease in the future.
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PMID:Mucolytics in cystic fibrosis. 1741 75

The rheology of saliva is highly important due to its influence on oral health and physiochemical processes within the oral environment. While the rheology of human whole saliva (HWS) is considered important for its functionality, its measurement is often performed erroneously and/or limited to the viscosity at a single shear rate. To ensure accurate rheological measurements, it is necessary to test HWS immediately after expectoration and to apply a thin layer of surfactant solution around the rim of the rheometer plates so that protein adsorption is minimized at the air-liquid interface. It is shown for the first time that the viscosity and viscoelasticity of HWS depends greatly upon the method of stimulation. Mechanical action stimulates slightly shear-thinning and relatively inelastic saliva, while acidic solutions (e.g. 0.25% citric acid) stimulate secretion of saliva that is highly elastic and shear-thinning. However, both acidic solutions and mechanical action stimulate similar volumes of saliva. For acid-stimulated saliva, the ratio of the primary normal stress difference to the shear stress is of order 100 and the viscosity at high shear rates is only marginally above that of water. This extremely high stress ratio for such a low viscosity fluid indicates that saliva's elastic properties dominate its flow behavior and may assist in facilitating lubrication within the oral cavity. It is anticipated that the variation in saliva rheology arises because the individual glands secrete saliva of different rheology, with the proportion of saliva secreted from each gland depending on the method of stimulation. The steady-shear rheology and linear viscoelasticity of HWS are described reasonably well using a FENE-P constitutive model and a 3-mode Maxwell model respectively. These models indicate that there are several long relaxation modes within saliva, possibly arising from the presence of large flexible macromolecules such as mucin glycoproteins.
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PMID:Viscoelasticity of human whole saliva collected after acid and mechanical stimulation. 1785 Nov 64

The motion of pseudo-sputum (20% solution of mucin) on a vibrating plate has been investigated using a function generator and an amplifier. Many finger-like liquid columns have appeared at appropriate frequencies (100-130 Hz) from a droplet of the solution on a vibrating plate. The viscosity of the mucin solution was measured using a capillary viscometer of the Maron-Krieger-Sisko type, and it was shown that the shear-thinning viscosity occurred in the lower frequency region contrary to the fact that the most abnormal viscosity of the rheological dilatancy fluid emerges in higher frequency than the frequency in which it behaves the normal one; the most important mechanical cause of this soliton-like phenomenon or the emergence of finger-like column and wrinkles on the surface of fluid is thought to be the rheological dilatancy (shear-thickening viscosity) of source liquid. In connection with this vibrating liquid column phenomenon, the spectrums of productive cough were also investigated, and it was proved that the effective low frequency vibration, which is a characteristic spectrum of productive cough, is essential for the expectoration and is a similar mechanism to the above-mentioned pug mechanism of the finger-like liquid columns seen on the vibrating plate.
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PMID:The dynamic motion of pseudo-sputum mucin solution on a vibrating plate. 1836 21

A 52-year-old black woman presented with a 5-year history of gradual swelling and slowed hair growth involving the vertex and both parietal regions of the scalp. Gradually, the swelling progressed to involve the entire scalp, only sparing a peripheral crown. She reported no history of trauma or medications. Slight pruritus of the involved area was the only accompanying symptom. There was no family history of a similar condition. Her past medical history included surgery for ovarian cysts, 10 years previously, and cholelithiasis. Physical examination revealed diffuse hair thinning and alopecia, more prominent along the vertex and parietal regions (Fig. 1a). There was no evidence of scalp inflammation, scaling, or increased hair fragility. The scalp was mildly tender on palpation and had a boggy, spongy consistency. The hairs which still remained in the involved areas were thin, short, and soft (Fig. 1b). The involved area was slightly hypopigmented when compared with adjacent noninvolved scalp. The rest of the physical examination was within normal limits. No abnormalities of the hair shaft were observed on microscopic examination of several plucked hairs. Laboratory investigations, including a complete blood cell count, blood chemistry, urinalysis, sedimentation rate, antinuclear antibodies, and serologic tests for syphilis, hepatitis B and C virus, and human immunodeficiency virus, were negative. A computed tomography scan of the skull demonstrated diffuse and regular thickening of subcutaneous fatty tissue of the scalp, disclosing a maximum scalp thickness of 15 mm at the vertex (Fig. 2). The biopsy from the vertex revealed a normal epidermis and dermis, with diffuse loss of hair follicles. The most striking feature consisted of a large increase in thickness of the subcutaneous fatty tissue (Fig. 3a). Pre-existing hair follicles were replaced by vertical fibrous tracts of lamellar fibroplasia with no inflammatory infiltrate (Fig. 3b). Adipocytes showed a normal size and shape, but the connective tissue septa, which are normally present separating the subcutaneous tissue into fat lobules, were lacking, and subcutaneous fatty tissue consisted of a continuous and diffuse sheet of mature adipocytes (Fig. 3c). Orcein stain revealed normal contents of elastic fibers with foci of condensation at the sites of disappeared pre-existing hair follicles (Fig. 3d). Colloidal iron and Alcian blue (pH 2.5) stains revealed no mucin deposits.
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PMID:Lipedematous alopecia: an uncommon clinicopathologic variant of nonscarring but permanent alopecia. 1847 57

This review elucidates several aspects on the behavior of charged polysaccharides and mucin. Viscosification of dilute aqueous solutions of hyaluronan (HA) occurs in the course of time at low shear flow, whereas shear thinning as time evolves is found at moderate shear rates. Hydrogen bonds and electrostatic interaction play an important role for the emergence of these features. No time effect of the viscosity is observed for semidilute HA solutions. A degradation of HA is observed at low and high pH and this effect continues over long times, and it is only in the approximate interval 5<pH<10 that HA is stable. Small angle neutron scattering (SANS) measurements on semidilute aqueous solutions of mucin at pH=7 reveal a fractal dimension of 1.4, and the effect of temperature is insignificant on the fractal structure. This suggests that the mucin chains on a semi-local dimensional scale are rod-like. From various experimental methods on solutions of mucin it was found that at pH values around 2 (uncharged polymer), the intensive hydrophobic interactions lead to large association complexes, whereas at pH>>2 the negative charges suppress the tendency of forming associations. At pH<2, the mucin chains are compressed and they are decorated by some positive charges. In the semidilute regime, a fragmented network is developed. The intense association in semidilute solutions of mucin at pH=2 is further supported by the results from rheo-small angle light scattering measurements. Effects of ionic strength on the radius of gyration (R(g)) for dilute solutions of HA (pH=7) and positively charged hydroxyethylcellulose (HEC(+)) are studied with the aid of Monte Carlo simulations, and essential features of the polyelectrolyte effect on R(g) are captured in the computer simulation. Strong interactions are observed in aqueous mixtures of an anionic polysaccharide (HEC(-)) and an oppositely charged surfactant (cetyltrimethylammonium bromide; CTAB); this gives rise to extensive associations and macroscopic phase separation is approached. The massive association complexes are disclosed in the SANS experiments by a pronounced upturn in the scattered intensity at low values of the wave vector.
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PMID:Characterization of polyelectrolyte features in polysaccharide systems and mucin. 1948 58


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