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Aims: Neoadjuvant chemotherapy (NAC) is often used to treat localised invasive breast cancer. Invasive mucinous carcinoma (IMC) is considered to be an indolent form of invasive breast cancer, and is rarely treated with NAC. We report the largest series of IMCs treated with NAC, and report a characteristic, but not well recognised, pattern of pathological response. Methods and results: Our series included seven patients with IMC treated with NAC. Three patients presented with locally advanced disease, three patients had tumours that were HER‐2/neu‐positive, and four patients had tumours with admixed mucinous and micropapillary features. Clinical and imaging assessment of response showed persistent and, in some cases, progressive disease, despite evidence of significant pathological response in these cases. Pathological assessment after NAC demonstrated marked reduction in tumour cellularity, but persistent space‐occupying mucin pools, showing acellular mucin in one case, <1% tumour cellularity in three cases, and 5–10% cellularity in three cases in both the treated breast and axillary lymph nodes. Conclusions: Persistent mass‐forming low‐cellular or acellular mucin pools can result in discordant clinical, imaging and pathological findings in IMC treated with NAC. [ABSTRACT FROM AUTHOR]

The association of lactic acid bacteria with mucosal surfaces plays important roles in the beneficial effects of these bacteria on human health, such as colonization of the gastrointestinal tract for pathogen antagonism. Previously, we found that the adhesion of Lactococcus lactis 7-1 to porcine gastric mucin was higher with fructose than with lactose, galactose or xylose as the carbon source. In this study, we examined the effect of growth conditions on the adhesion of strain 7-1 grown on fructose. Medium components affect the adhesion: the adhesion of strain 7-1 grown with sodium acetate was higher than that without it. The enhancement of adhesion by sodium acetate was not observed under aerobic conditions. Cellular properties grown with or without sodium acetate were characterized: strain 7-1 grown with sodium acetate had similar sugar contents, and different fatty acid composition to those grown without it. Strain 7-1 grown with sodium acetate showed significantly lower cell yield and significantly higher hydrophobicity than those grown without it, which is associated with higher adhesion. Fructose and sodium acetate are frequently used in the food industry; this study may reveal a simple way to enhance the adhesion of lactic acid bacteria by growing them with these substances. [ABSTRACT FROM AUTHOR]

Herein, we systematically investigate the origin of astringent mouthfeel when we eat unripe fruits, drink coffee or tea, from the perspective of lubrication by simulating the dynamic weak interaction on the tongue with model protein (mucoprotein, MP) and polyphenolic compounds (tannic acid, TA). Astringency was due to the protein-mediated lubrication failure when encountering polyphenolic molecules that normally exist, for example in unripe fruits, coffee, tea. The underlying molecular mechanism of oral tribology is widely present in nature and enables us to engineer a tongue-like polyacrylamide composite hydrogel that exhibits high TA sensitivity and to develop a scientific strategy for catching slippery fish using TA-containing gloves. These results provide novel and useful insights into the failure of biological boundary lubrication on soft tissue surface with the adsorbed proteins. [ABSTRACT FROM AUTHOR]

Invasive carcinoma of no special type (NST) or ductal carcinoma is the largest group of invasive breast cancers. Invasive lobular carcinoma (ILC) is the second most common histological type; it comprises 5%–15% of all invasive breast cancers. Historically, lobular neoplasia and invasive lobular carcinoma may produce intracellular mucin that pushes the nucleus to one side, creating the characteristic signet ring cell morphology. The extracellular mucin secretion is essentially described in mucinous breast carcinoma. Mucinous differentiation can be seen in small areas of NST carcinoma, but recently a few cases of invasive lobular carcinoma with extracellular mucin are reported in the literature. It is important for pathologists to recognize this new entity because it mimics a NST carcinoma, as such a diagnosis may require a different approach in clinical management and surveillance. We report a new case of ILC with extracellular mucin and a review of the literature. [ABSTRACT FROM AUTHOR]

Background and objective Secreted mucins play a key role in antibacterial defence in the airway, but have not previously been characterized in non-cystic fibrosis (CF) bronchiectasis patients. We aim to investigate the relationship between secreted mucins levels and the presence of bacterial colonization due to potentially pathogenic microorganisms ( PPM) in the airways of stable bronchiectasis patients. Methods Clinically stable bronchiectasis patients were studied prospectively at two centres. Patients with other pulmonary conditions were excluded. Spontaneous sputum was subject to bacterial culture, and secreted mucins ( MUC2, MUC5AC and MUC5B) were measured in sputum supernatants by ELISA. Results A total of 50 patients were included. PPM were identified from sputum samples in 30 (60%), with P seudomonas aeruginosa ( n = 10) and H aemophilus influenzae ( n = 10) as the most common PPM. There were no baseline differences among airway colonized and non-colonized patients. Patients with airways colonized by PPM presented higher levels of airway MUC2. No differences in MUC5AC levels were found among groups, whereas MUC5B levels were undetectable. Patients with P . aeruginosa colonization expressed the highest levels of MUC2. High levels of MUC2 and MUC5AC are also correlated with disease severity using the Bronchiectasis Severity Index. Conclusions Airway MUC2 levels were higher in bronchiectasis patients colonized with PPM compared with those without airway colonization, especially in patients with P . aeruginosa. These findings suggest that airway-secreted mucins levels may play a role in the pathogenesis of airway infection in non-CF bronchiectasis. [ABSTRACT FROM AUTHOR]

Mucins are a class of highly O-glycosylated proteins found on the surface of cells in epithelial tissues. O-Glycosylation is crucial for the functionality of mucins and changes therein can have severe consequences for an organism. With that in mind, the elucidation of interactions of carbohydrate binding proteins with mucins, whether in morbidly altered or unaltered conditions, continue to shed light on mechanisms involved in diseases like chronic inflammations and cancer. Despite the known importance of type-1 and type-2 elongated mucin cores 1-4 in glycobiology, the corresponding type-1 structures are much less well studied. Here, the first chemical synthesis of extended mucin type-1 O-glycan core 1-3 amino acid structures based on a convergent approach is presented. By utilizing differentiation in acceptor reactivity, shared early stage Tn- and T-acceptor intermediates were elongated with a common type-1 [β- D-Gal-1,3-β- D-GlcNAc] disaccharide, which allows for straightforward preparation of diverse glycosylated amino acids carrying the type-1 mucin core 1-3 saccharides. The obtained glycosylated 9-fluorenylmethoxycarbonyl (Fmoc)-protected amino acid building blocks were employed in synthesis of type-1 mucin glycopeptides, which are useful in biological applications. [ABSTRACT FROM AUTHOR]

Don't take this antivitamin! 2‐Phenylethynylcobalamin (see picture) was prepared in a newly developed radical reaction using cob(II)alamin and 1‐iodo‐2‐phenylethyne. It has an exceptionally short organometallic bond and is a remarkably light‐stable and heat‐resistant organometallic cobalamin. It is bound well by two important proteins of the human B12 transport system and has properties that are as expected for a new type of an “antivitamin B12”. [ABSTRACT FROM AUTHOR]

Citation Iwasawa Y, Kawana K, Fujii T, Schust DJ, Nagamatsu T, Kawana Y, Sayama S, Miura S, Matsumoto J, Adachi K, Hyodo H, Yamashita T, Kozuma S, Taketani Y. A possible coagulation-independent mechanism for pregnancy loss involving β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012; 67: 54-65 Problem β2glycoprotein1 (β2GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti-β2GP1 antibodies can interact with phosphatidylserine (PS)-bearing CD1d on trophoblast cells and induce local inflammation. Methods CD1d-bearing choriocarcinoma cells were used in flow cytometry and immunoprecipitation experiments. CD1d-mediated cytokine induction was assessed using antibody cross-linking. Cytokine production during co-culture of decidual lymphocytes with CD1d-bearing cells was also examined. Results Trophoblast surface-expressed CD1d forms a complex with PS-bound β2GP1. Anti-β2GP1 mAb cross-linking causes IL12p70 release from CD1d-bearing cells. IL12p70 release from CD1d-bearing trophoblast cells was also induced during co-culture with human decidual lymphocytes. The addition of anti-β2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFNγ secretion from decidual lymphocytes was also induced during co-culture with anti-β2GP1 mAbs. Conclusions β2GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism. [ABSTRACT FROM AUTHOR]

Mucus hypersecretion is an important manifestation in patients with chronic obstructive pulmonary diseases (COPD). Cigarette smoke is importantly implicated in the pathogenesis of COPD. Previous studies have shown that cigarette smoke-induced MUC5AC (a major component of airway mucus) expression involving ErbB1 (EGF receptor) signalling pathway. Recently, it has been reported that cigarette smoke induces ErbB3 activation in airway epithelia to secret mucus, and the ligand of ErbB3, neuregulin (NRG) 1β, induces MU5AC expression in human bronchial epithelial cells. In the present study, we have suggested that NRG1β/ErbB3 signalling is activated by cigarette smoke, resulting in the activation of a variety of signal cascade pathways, leading to mucin production in human bronchial epithelial (16HBE) cells. We show that cigarette smoke increases NRG1β release, ErbB3 phosphorylation and MUC5AC production. These effects are prevented by an ErbB3-neutralizing antibody and by specific knockdown using small interfering RNA (siRNA) for NRG1β, implicating NRG1β-dependent ErbB3 activation in the responses. Cigarette smoke activates ERK1/2, c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3-K) signalling pathways, which are also inhibited by an ErbB3-neutralizing antibody and NRG1β siRNA, indicating the regulation of cigarette smoke-activated pathways by NRG1β/ErbB3 signalling. Furthermore, pre-treatments with metalloprotease inhibitor (TNF-α protease inhibitor-1) and specific knockdown of TNF-α-converting enzyme (TACE) with TACE siRNA prevented cigarette smoke-induced NRG1β release, ErbB3 phosphorylation and mucin production, suggesting the role of TACE in cigarette smoke-mediated NRG1β/ErbB3 signalling activation. These results suggest that NRG1β/ErbB3 signalling regulates cigarette smoke-induced mucin overproduction via the MAPK and PI3K signal pathways in 16HBE cells. [ABSTRACT FROM AUTHOR]

MUC4 is a heterodimeric membrane mucin, composed of a mucin subunit ASGP-1 (MUC4α) and a transmembrane subunit ASGP-2 (MUC4β), which has been implicated in the protection of epithelial cell surfaces. In the rat stratified corneal epithelium Muc4 is found predominantly in the most superficial cell layers. Since previous studies in other tissues have shown that Muc4 is regulated by TGF-β via a proteosomal degradation mechanism, we investigated the regulation of corneal Muc4 in stratified cultures of corneal epithelial cells. Application of proteosome or processing inhibitors led to increases in levels of Muc4, particularly in the basal and intermediate levels of the stratified cultures. These changes were accompanied by increases in Muc4 ubiquitination, chaperone association and incorporation into intracellular aggresomes. In contrast, treatment with TGF-β resulted in reduced levels of Muc4, which were reversed by proteosome inhibition. The results support a model in which Muc4 precursor is synthesized in all layers of the corneal epithelium, but Muc4 is degraded in basal and intermediate layers by a proteosomal mechanism at least partly dependent on TGF-β inhibition of Muc4 processing. J. Cell. Physiol. 223: 209–214, 2010. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We present a 49-year-old man with type I erythromelalgia, demonstrating a newly reported histological feature of striking perivascular mucin. There is a single previously reported case in the literature describing these histological features. This patient had a comorbid history of primary myelofibrosis diagnosed 2 years prior to his presentation. [ABSTRACT FROM AUTHOR]

Mucins are the most abundant high molecular weight glycoproteins in mucus. Their nature and glycosylation content dictates the biochemical and biophysical properties of viscoelastic secretions, pointing out an important role in diverse biological functions, such as differentiation, cell adhesions, immune responses, and cell signaling. Mucins are expressed in tubular organs by specialized epithelial cells in the body. Their aberrant expression is well documented in a variety of inflammatory or malignant diseases. From a prognosis point of view, their expression and alterations in glycosylation are associated with the development and progression of malignant diseases. Therefore, mucins can be used as valuable markers to distinguish between normal and disease conditions. Indeed, this alteration in glycosylation patterns generates several epitopes in the oligosaccharide side chains that can be used as diagnostic and/or prognostic markers. Furthermore, these characteristic tumor-associated epitopes are extensively used as appropriate immunotargets of malignant epithelial cells. Therefore, in an effort to detect and treat cancer at the earliest stage possible, mucins are analyzed as potential markers of disease for diagnosis, progression, and for therapeutic purposes. In this review, we focused on the current status of the distribution of mucins in normal and pathologic conditions and their clinical use both in cancer diagnosis and therapeutics treatments. [ABSTRACT FROM AUTHOR]

The presence of mucin in infiltrating lobular carcinomas has been described as occurring exclusively in an intracytoplasmic location. To the best of the authors' knowledge, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature. Herein is presented a case of lobular carcinoma with extracellular mucin in a 60-year-old female patient, who also had a contralateral ductal carcinoma of the cribriform type. Histologically the tumor had the classical appearance of infiltrating lobular carcinoma with signet ring cells and ‘Indian file’ infiltration of the stroma as well as pools of extracellular mucin. It is of great importance to appropriately classify breast carcinomas as ductal or lobular in origin due to the different treatment, prognosis, and clinical behavior of these lesions. The present finding opens the door for discussion of the current knowledge concerning histological variants of lobular carcinoma and should alert pathologists to the fact that the presence of extracellular mucin in an otherwise classical infiltrating lobular carcinoma does not preclude this diagnosis. [ABSTRACT FROM AUTHOR]

Background: There is strong evidence that reduced exposures to microbial compounds triggering innate immune responses early in life are critical for the development of allergic illnesses. The underlying mechanisms remain unknown, but will include T-cell responses either along T helper type 1 (Th1)/Th2 pathways or via T regulatory and Th17 cells. Yet, little is known about innate immune responses and the function of T regulatory/Th17 cells at birth. The aim of this study was to investigate T-cell responses to innate (Lipid A/LpA, peptidoglycan/Ppg) and adaptive (phytohemagglutinin) stimuli at birth and to compare these findings with adult immune responses. Methods: Cord and peripheral blood mononuclear cells including T regulatory and Th17 cells from 25 neonates and 25 adults were examined for proliferation, cytokine secretion, surface, mRNA expression and functional suppression assays. Results: Proliferation and cytokine responses to innate stimuli were less mature at birth than in adulthood. T regulatory and Th17 cells were less expressed in cord than in adult blood (Ppg-induced Foxp3, P = 0.001, LpA-induced CD4+ CD25+ high, P = 0.02; Th17 : P < 0.0001). Mitogen-induced suppression of T-regulatory cells on T-effector cell function was less efficient in cord than in adult blood ( P = 0.01). At both ages, Th17 cells were correlated with Th1/Th2 cells ( P < 0.01), but not with interleukin-10 secretion following innate-stimulation. Conclusion: Innate immune responses are immature at birth. Furthermore, the function of T regulatory and Th17 cells is impaired. Th17 cells in association with Th1/Th2 cells may be involved in early immuno-modulation. Potent innate immune stimulation early in life can potentially contribute to protection from allergic diseases. [ABSTRACT FROM AUTHOR]

The article presents a study on the expression of mucins (MUC) in synovial tissue (ST) and their role in arthritis. Mucins are a family of heavily glycosylated proteins that protect epithelial membranes and are used as ligands for cell adhesion. The study performed immunohistochemistry and reverse transcriptase-polymerase chain reaction to determine expression patterns of MUC1, MUC2, MUC3 and MUC5AC in rheumatoid arthritis, osteoarthritic and normal human ST. It was found that MUC3 was expressed in synovial lining cells, macrophages and fibroblasts.

The therapeutic effects of intravenous immunoglobulins (IVIGs) on different chronic inflammatory and autoimmune diseases is well appreciated, though clinical studies with high-evidence levels are largely missing. Similar to the broad spectrum of diseases and their underlying etiopathogenic background, the mechanisms of action seem heterogenous and multifold. Several studies addressing in vitro and in vivo effects of IVIG on various immunological parameters have been described with partly contradictory results. In this study immunoglobulins and stabilizers present in commercial IVIG preparations were studied in regard to the in vitro proliferation and cytokine production of peripheral blood mononuclear cells when stimulated with phytohemagglutinin (PHA), interleukin 2, and tetanus toxoid. Whereas the immunoglobulins stimulate the proliferation of PBMCs and decrease IFNγ secretion, stabilizers of IVIG seem to inhibit the proliferation of PBMCs while increasing the secretion of IFN γ. These effects have to be taken into account when balancing the impact of IVIG dosage and infusion intervals and relating them to clinical side effects and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Allergic fungal sinusitis is a non-invasive disease characterized by pansinusitis with nasal polyps, with most causative agents being members of the dematiaceous fungi. Reported herein is the ninth Japanese case of allergic fungal sinusitis; an Alternaria species was culturally identified as the etiological agent. The present patient, a 32-year-old man, presented with multiple sinusitis and nasal polyps. Allergic mucin, which is a histological hallmark of this disease, was examined intraoperatively on frozen section. Although characteristic histology, including laminated masses of mucin and aggregates of eosinophils, was seen in HE-stained sections, fungal hyphae were scarce and recognized merely as clear spaces. Because fluorescent stilbene derivatives seem useful for the rapid detection of fungi, Fungiflora Y, a commercially available staining kit that includes a fluorescent stilbene derivative, was applied to the sections, and hyphae were successfully visualized using a fluorescence microscope. This stain takes only several minutes to perform. It is concluded that Fungiflora Y should be used when fungal elements are hard to find on HE stain, especially in cases in which rapid detection of fungus is requested. [ABSTRACT FROM AUTHOR]

To cope with life-threatening high osmolarity, yeast activates the high-osmolarity glycerol (HOG) signaling pathway, whose core element is the Hog1 MAP kinase cascade. Activated Hog1 regulates the cell cycle, protein translation, and gene expression. Upstream of the HOG pathway are functionally redundant SLN1 and SHO1 signaling branches. However, neither the osmosensor nor the signal generator of the SHO1 branch has been clearly defined. Here, we show that the mucin-like transmembrane proteins Hkr1 and Msb2 are the potential osmosensors for the SHO1 branch. Hyperactive forms of Hkr1 and Msb2 can activate the HOG pathway only in the presence of Sho1, whereas a hyperactive Sho1 mutant activates the HOG pathway in the absence of both Hkr1 and Msb2, indicating that Hkr1 and Msb2 are the most upstream elements known so far in the SHO1 branch. Hkr1 and Msb2 individually form a complex with Sho1, and, upon high external osmolarity stress, appear to induce Sho1 to generate an intracellular signal. Furthermore, Msb2, but not Hkr1, can also generate an intracellular signal in a Sho1-independent manner. [ABSTRACT FROM AUTHOR]

Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens, are among of the most specific human cancer-associated structures. These antigens are involved in several types of receptor-ligand interactions, and they are potential targets for immunotherapy. In the last few years several simple mucin-type O-glycan antigens were identified in different species belonging to the main two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in Trypanosoma cruzi. These results are of interest to understand new aspects in parasite glycoimmunology and may help identify new biological characteristics of parasites as well of the host-parasite relationship. Considering that different groups reported a negative correlation between certain parasite infections and cancer development, we could hypothesize that simple mucin-type O-glycosylated antigens obtained from parasites could be good potential targets for cancer immunotherapy. IUBMB Life, 59: 269-273, 2007 [ABSTRACT FROM AUTHOR]

Mucin, a major component of mucus, is a highly O-glycosylated, high-molecular-mass glycoprotein extensively involved in the physiology of gastrointestinal mucosa. To detect and characterize mucins derived from site-specific mucous cells, we developed a monoclonal antibody, designated PGM34, by immunizing a mouse with purified pig gastric mucin. The reactivity of PGM34 with mucin was inhibited by periodate treatment of the mucin, but not by trypsin digestion. This suggests that PGM34 recognizes the carbohydrate portion of mucin. To determine the epitope, oligosaccharide-alditols obtained from pig gastric mucin were fractionated by successive gel-filtration, ion-exchange, and normal-phase HPLC, and tested for reactivity with PGM34. Two purified oligosaccharide-alditols that reacted with PGM34 were obtained. Their structures were determined by NMR spectroscopy as Fucα1–2Galβ1–4GlcNAc(6SO3H)β1–6(Fucα1–2Galβ1–3)GalNAc-ol and Fucα1–2Galβ1–4GlcNAc(6SO3H)β1–6(Galβ1–3)GalNAc-ol. None of the defucosylated or desulfated forms of these oligosaccharides reacted with PGM34. Thus, the epitope of PGM34 was determined as the Fucα1–2Galβ1–4GlcNAc(6SO3H)β- sequence. Immunohistochemical examination of rat gastrointestinal tract showed that PGM34 stained surface mucous cells close to the generative cell zone in the gastric fundus and goblet cells in the small intestine, but only slightly stained antral mucous cells in the stomach. These data, taken together, show that PGM34 is a very useful tool for elucidating the role of mucins with characteristic sulfated oligosaccharides. [ABSTRACT FROM AUTHOR]

Background and purpose:Extracts of Plumbago zeylanica containing suberosin exhibit anti-inflammatory activity. We purified suberosin from such extracts and studied its effects on a set of key regulatory events in the proliferation of human peripheral blood mononuclear cells (PBMC) stimulated by phytohemagglutinin (PHA).Experimental approach:Proliferation of PBMC in culture was measured by uptake of 3H-thymidine; production of cytokines and cyclins by Western blotting and RT-PCR. Transcription factors NF-AT and NF-κB were assayed by immunocytochemistry and EMSA.Key results:Suberosin suppressed PHA-induced PBMC proliferation and arrested cell cycle progression from the G1 transition to the S phase. Suberosin suppressed, in activated PBMC, transcripts of interleukin-2 (IL-2), interferon-γ (IFN-γ), and cyclins D3, E, A, and B. DNA binding activity and nuclear translocation of NF-AT and NF-κB induced by PHA were blocked by suberosin. Suberosin decreased the rise in intracellular Ca2+ concentration ([Ca2+]i) in PBMC stimulated with PHA. Suberosin did not affect phosphorylation of p38 and JNK but did reduce activation of ERK in PHA-treated PBMC. Pharmacological inhibitors of NF-κB, NF-AT, and ERK decreased expression of mRNA for the cyclins, IL-2, and IFN-γ and cell proliferation in PBMC activated by PHA.Conclusions and Implications:The inhibitory effects of suberosin on PHA-induced PBMC proliferation, were mediated, at least in part, through reduction of [Ca2+]i, ERK, NF-AT, and NF-κB activation, and early gene expression in PBMC including cyclins and cytokines, and arrest of cell cycle progression in the cells. Our observations provide an explanation for the anti-inflammatory activity of P. zeylanica.British Journal of Pharmacology (2007) 150, 298–312. doi:10.1038/sj.bjp.0706987; published online 18 December 2006 [ABSTRACT FROM AUTHOR]

This 77-year-old woman with a rapidly enlarging chordoid meningioma first noticed a growing, non-pulsatile, non-painful soft mass in the left temporal region after a head trauma 2 years earlier. Neuroimaging showed a homogeneously enhanced osteolytic mass lesion in the left temporal bone. Surgery revealed an extradural tumor without significant adhesions. Histopathologically it was a meningioma with features reminiscent of chordoma. Most of the tumor cells contained mucin-rich chordoid elements. Immunohistochemically, the lesion was positive for vimentin and epithelial membranous antigen; it was negative for cytokeratin and S-100 protein. Based on these findings a diagnosis of chordoid meningioma was made. We posit that the rapid enlargement of the tumor over a relatively short period was attributable to its high mucin-producing activity. [ABSTRACT FROM AUTHOR]

Background Controversy exists concerning the efficacy of acid suppressants in the regression of Barrett's oesophagus. Aim To evaluate the effect of proton pump inhibitors on cyclooxygenase-2 expression, cellular proliferation and apoptosis in Barrett's oesophagus with different mucin phenotypes. Methods Four hundred and sixty-six biopsy samples of Barrett's oesophagus from 358 non-treatment patients and 81 from 61 chronic proton pump inhibitor users were immunohistochemically examined using anti-cyclooxygenase-2 protein, anti-proliferating cell nuclear antigen and anti-single stranded DNA antigens in both mucin phenotypes of Barrett's oesophagus. Results Prevalence of the cyclooxygenase-2 expression pattern did not significantly differ between the non-treatment and proton pump inhibitor users. In those using proton pump inhibitors, significant suppression of the proliferating cell nuclear antigen index was found in Barrett's oesophagus with the gastric-predominant mucin phenotype, but not with the intestinal-predominant mucin phenotype. Apoptosis indices in chronic proton pump inhibitor users did not significantly differ between the two mucin phenotypes. Conclusions Proton pump inhibitors suppress cellular proliferation in Barrett's oesophagus with the gastric-predominant mucin phenotype but not in that with the intestinal-predominant mucin phenotype. This finding may at least partly explain the ongoing controversy surrounding the notion that all cases of Barrett's oesophagus respond to acid-suppressive therapy. [ABSTRACT FROM AUTHOR]

The mucin MUC7 is a glycoprotein that plays a role in bacterial clearance and has candidacidal activity. There are two common allelic forms with 5 or 6 tandem repeats (TR) of a 23 amino acid motif within the highly glycosylated (mucin) domain. The MUC7*5 allele has previously been shown to be less prevalent in patients with asthma, suggesting a protective role in respiratory function. Here we report the characterisation of other frequent genetic variation within and in the vicinity of the gene MUC7. A total of 26 polymorphisms were identified of which 5 are located in transcribed regions. A subset of 8 polymorphisms was selected to represent the major haplotypes, and allelic association was studied in individuals of Northern European ancestry, including known asthmatics. There was low haplotype diversity and strong association between each of the loci, and the MUC7* 5 allele-carrying haplotype remained the one most strongly associated with asthma. Five of these polymorphisms have also been tested in the 1946 longitudinal birth cohort, for whom developmental, environmental and respiratory health data are available. We show that the haplotype carrying MUC7*5 is associated with higher FEV1 at 53 years, reduced age-related decline of FEV1, and also reduced incidence of wheeze. [ABSTRACT FROM AUTHOR]

Background Mucus hyper-secretion is a feature of several airways diseases such as chronic rhinosinusitis, asthma, and cystic fibrosis (CF). Since mucins are major components of mucus, the knowledge of their distribution and regulation in nasal tissues is likely to improve mucus hyper-secretion therapy. Objective The aim of this study was to evaluate and compare mucin gene expression at epithelial and glandular levels, and to identify potential mucin expression patterns for specific upper airways pathologies. Methods Immunohistochemistry for MUC1, MUC2, and MUC4–MUC8 mucins was performed on healthy nasal mucosa (NM; n=12), bilateral nasal polyps (NP; n=38), NP from CF patients ( n=10), and antrochoanal (AC) polyps ( n=11). MUC2, MUC4, MUC5AC, and MUC6 mRNA expression were also analysed by in situ hybridization. Results MUC1, MUC4, and MUC5AC mucins were highly expressed in the epithelium and their expression pattern was similar in all NP types, MUC1 and MUC4 being increased and MUC5AC decreased compared with NM. MUC8 was highly detected at both epithelial and glandular levels with marked variability between groups. MUC5B was mainly detected in glands and the expression in all polyp types was higher than in NM. Moreover, MUC5B expression was higher in NP epithelia from CF patients than in bilateral NP and healthy NM. Although MUC2 expression was low, especially in AC polyps, it was detected in most samples. In NM, MUC6 and MUC7 were scarcely detected and MUC7 expression was restricted to glands. Conclusions These results suggest that NP have a different pattern of mucin expression than healthy NM and that CF polyps (increased MUC5B) and AC polyps (decreased MUC2) have a different mucin expression pattern than bilateral NP. [ABSTRACT FROM AUTHOR]

Gastric carcinomas (GC) are classified into four phenotypes on the basis of the mucin expression profile: G type (gastric or foveolar phenotype), I type (intestinal phenotype), GI type (intestinal and gastric mixed phenotype) and N type (neither gastric nor intestinal phenotype). Immunohistochemistry was used to examine the expression of epidermal growth factor receptor (EGFR), E-cadherin, liver–intestine (LI)-cadherin, CD44v9 and p53 and correlation of these molecules with mucin phenotype and tumor stage was evaluated. Overexpression of EGFR and LI-cadherin, reduced expression of E-cadherin and abnormal expression of p53 were observed more frequently in advanced GC than in early GC. Among I-type GC, overexpression of EGFR and reduced expression of E-cadherin were observed more frequently in advanced tumors than in early tumors. Among G-type GC, reduced expression of E-cadherin was significantly associated with advanced tumors. With respect to the relationship between mucin phenotype and expression of cancer-related molecules, overexpression of LI-cadherin was observed more frequently in I-type (12/25, 48.0%) than in G-type (1/14, 7.1%) GC. I-type GC tended to express LI-cadherin more frequently than GI-type GC. These results provide insights into the molecular characteristics of the distinct mucin phenotype of differentiated-type GC and suggest that LI-cadherin may contribute to the biological behavior of I-type GC. [ABSTRACT FROM AUTHOR]

Objective: Circulating levels of KL-6, a high MW glycoprotein (MUC1 mucin), are elevated in a majority of patients with a number of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF). However, KL-6 levels vary from patient to patient. The aim of the present study was to determine whether the serum KL-6 level at the time of diagnosis predicts prognosis in IPF. Methods: The relationship between clinical variables and prognosis in 27 patients with IPF were analysed retrospectively. The diagnosis was made by histological examination ( n = 16) or on clinical findings including high-resolution CT scanning ( n = 11). All patients were followed up for at least 3 years. Variables such as age, FVC%, PaO2 at rest, initial LDH level, C-reactive protein and KL-6 were used for analysis. Results: At the cut-off level determined by receiver operating characteristic curves, LDH and KL-6 showed a significant correlation with the patient's prognosis by univariate analysis. However, multivariate analysis revealed that only KL-6 was a predictor of prognosis. The patients were categorized by their serum KL-6 levels (as above or below the cut-off level of 1000 U/mL) and their survival estimated using the Kaplan–Meier method. The difference in median survival between the two groups was significant. The median survival of patients with low KL-6 was more than 36 months, whereas that of patients with high KL-6 was only 18 months. Conclusion: These results suggest that initial evaluation of serum KL-6 level can predict survival in patients with IPF. [ABSTRACT FROM AUTHOR]

Previous studies have shown that peptides derived from the N-terminal region of the low molecular mass human salivary mucin, MUC7, possess potent in vitro cidal activity against Candida albicans and other medically important fungi. MUC7 12-mer (residues 40–51 of the parent MUC7) peptide, having the optimal size and a net charge of +6, was found to be anticandidal in human saliva (clarified and unclarified), and its candidacidal potency was found to be superior to that of histatin 5 12-mer (Hsn5 12-mer). We have, therefore, explored the candidacidal potency of MUC7 12-mer (l andd isomers) and Hsn5 12-mer peptides in vivo. In vitro killing assay was performed to establish killing activity of the peptides against C. albicans prior to in vivo experiments. A murine model of oral candidiasis that has the characteristics of oral thrush in humans was employed for the in vivo studies, based on a previous protocol. Upon candidal induction, antifungal treatment application using agents emulsified in Pluronic F127 was performed for six consecutive days. Amphotericin B and clotrimazole emulsified in the same delivery system were used as positive control drugs. Candidacidal efficacy was evaluated microbiologically and histopathologically. Results demonstrated a considerable reduction of fungal burden by the MUC7 12-mer peptides (l andd), comparable to control drugs, and this effect was statistically significant, unlike the effect seen with Hsn5 12-mer. Murine oral candidiasis model employed in this study is suitable to test the candidacidal agents employing Pluronic F127. In conclusion, MUC7 12-mer appears to be a promising candidate as an antifungal agent for oral candidiasis. [ABSTRACT FROM AUTHOR]

Secretion of mucins and exudation of plasma are distinct processes of importance to innate immunity and inflammatory disease. Yet, little is known about their relation in human airways. The objective of the present study was to use the human nasal airway to determine mucinous secretion and plasma exudation in response to common challenge agents and mediators. Ten healthy volunteers were subjected to nasal challenge-lavage procedures. Thus, the nasal mucosa was exposed to increasing doses of histamine (40 and 400 μg ml−1), methacholine (12·5 and 25 mg) and capsaicin (30 and 300 ng ml−1). Fucose was selected as a global marker of mucinous secretion and α2-macroglobulin as an index of exudation of bulk plasma. All challenge agents increased the mucosal output of fucose to about the same level ( P<0·01–0·05). Once significant secretion had been induced the subsequently increased dose of the challenge agent, in the case of histamine and methacholine, failed to further increase the response. Only histamine increased the mucosal output of α2-macroglobulin ( P<0·01). We conclude that prompt but potentially rapidly depleted mucinous secretion is common to different kinds of airway challenges, whereas inflammatory histamine-type mediators are required to produce plasma exudation. Along with the acknowledged secretion of mucins, a practically non-depletable, pluripotent mucosal output of plasma emerges as an important component of the innate immunity of human airways. [ABSTRACT FROM AUTHOR]

The differential diagnosis of salivary gland carcinoma is often difficult because of the confusing histopathological features of the different types of salivary gland carcinomas. The expression of MUC3, MUC5AC, MUC6, cytokeratin (CK)7 and CK20 was studied in 20 mucoepidermoid carcinomas (MEC), 20 adenoid cystic carcinomas (AdCC), and 11 acinic cell carcinomas (ACC). All the cases (51/51, 100%) were positive for CK7, but they were not positive for CK20. All the cases (100%) of the MEC were positive for MUC5AC, while all MEC (100%) were negative for MUC3. Only two cases (10%) were positive for MUC6. All cases (100%) of AdCC were negative for MUC3, MUC5AC and MUC6. Eight cases (73%) of ACC were positive for MUC3, but all the cases (100%) were negative for MUC5AC and MUC6. It is concluded that the positive expression of MUC5AC is very unique to MEC, and that the positive expression of MUC3 is very unique to ACC. These findings will be very useful for the differential diagnosis of the salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

In vivo Listeria monocytogenes infection results in the massive release of mucus by goblet cells into the lumen of the intestine. We have previously reported that apical infection by L. monocytogenes is followed by listeriolysin O (LLO)-dependent stimulation of mucus exocytosis, and the upregulation of the MUC genes. Here, we report that L. monocytogenes EGD wild-type bacteria enter cultured human polarized, mucin-secreting, HT29-MTX cells apically by an InlA-dependent mechanism. The LLO-induced increase in mucin secretion together with an increase in transcription of the MCU4 and MUC12 genes encoding for membrane-bound mucins, results in the inhibition of the cell-entry of L. monocytogenes into mucin-secreting, HT29-MTX cells. Moreover, we report that sialic acid residues in mucins are crucial for the inhibition of L. monocytogenes internalization. Based on these findings, we suggest that the LLO-induced mucin exocytosis and upregulation of the MUC genes encoding for membrane-bound mucins constitute a host cell defence response that inhibits the cell-entry of L. monocytogenes. [ABSTRACT FROM AUTHOR]

Primary vaginal adenocarcinomas are rare neoplasms. Herein is reported a case of primary vaginal mucinous adenocarcinoma with an interesting mucin profile, presumably arising from a lesion of adenosis in a patient withoutin uteroexposure to diethylstilbesterol (DES). The patient, a 44-year-old woman, had undergone vaginal total hysterectomy 10 years previously for myoma uteri corporis. The histological features of the vaginal intramural tumor found in this patient resembled those of mucinous adenocarcinoma of the endocervical type. Therefore, it was necessary to determine whether or not the tumor was metastatic from an occult cervical adenocarcinoma. However, the adenocarcinoma cells of the present case did not contain sulfomucin at all, being different from most mucinous adenocarcinoma cells of the endocervical type. Moreover, there were foci of adenosis adjacent to the adenocarcinoma foci, which also did not contain sulfomucin. These findings indicate that the mucinous adenocarcinoma arose from vaginal adenosis. Further studies are necessary to investigate whether lack of sulfomucin expression is a characteristic feature of vaginal adenosis. [ABSTRACT FROM AUTHOR]

The membrane-tethered mucins are cell surface-associated dimeric or multimeric molecules with extracellular, transmembrane and cytoplasmic portions, that arise from cleavage of the primary polypeptide chain. Following the first cleavage, which may be cotranslational, the subunits remain closely associated through undefined noncovalent interactions. These mucins all share a common structural motif, the SEA module that is found in many other membrane-associated proteins that are released from the cell surface and has been implicated in both the cleavage events and association of the subunits. Here we examine the SEA modules of three membrane-tethered mucins, MUC1, MUC3 and MUC12, which have significant sequence homology within the SEA domain. We previously identified the primary cleavage site within the MUC1 SEA domain as FRPG/SVVV a sequence that is highly conserved in MUC3 and MUC12. We now show by site-directed mutagenesis that the F, G and S residues are important for the efficiency of the cleavage reaction but not indispensable and that amino acids outside this motif are probably important. These data are consistent with a new model of the MUC1 SEA domain that is based on the solution structure of the MUC16 SEA module, derived by NMR spectroscopy. Further, we demonstrate that cleavage of human MUC3 and MUC12 occurs within the SEA domain. However, the SEA domains of MUC1, MUC3 and MUC12 are not interchangeable, suggesting that either these modules alone are insufficient to mediate efficient cleavage or that the 3D structure of the hybrid molecules does not adequately recreate an accessible cleavage site. [ABSTRACT FROM AUTHOR]

The objectives of this study were: (i) to determine tear film breakup times (BUTs) in young healthy cats; (ii) to determine tear film BUTs in feline eyes within 8–20 h following general anesthesia; (iii) to determine if tear film BUTs vary significantly preoperatively when compared with values obtained 8–20 h postoperatively; (iv) to determine if Schirmer tear test (STT) values correlate with tear film BUTs in young healthy cats; and (v) to determine if the isolation of particular etiologic agents from conjunctival swabs of healthy cats affects tear film BUTs. We studied eighteen healthy Domestic Short-haired (n = 14) and Domestic Long-haired (n = 4) cats, with normal ocular examinations, ranging in age from 0.5 to 3 years. Complete ophthalmic examinations, including tear film BUTs, were performed on all cats. Conjunctival swabs from each eye of all cats and blood samples from all cats were collected and submitted for polymerase chain reaction screening for feline herpes virus,Chlamydophila felis,Mycoplasmaspp., and calicivirus. In 10 of 18 cats, STT values and tear film BUTs were measured before general anesthesia was administered and again within 8–20 h following the end of anesthesia. Mean preanesthesia tear film BUTs for all 18 cats were 17.4 ± 4.6 s OD and 16.0 ± 4.5 s OS. Mean postanesthesia tear film BUT results were 12.5 ± 4.3 and 13.1 ± 4.0 s OD and OS, respectively. Postanesthesia tear film BUTs were significantly more rapid than those measured before anesthesia (OD only). There was also a positive correlation, both before and after anesthesia, between STT values in both eyes (OU) and tear film BUTs OU. The isolation or lack of isolation of conjunctival microorganisms using PCR did not significantly affect tear film BUTs. Mean tear film BUT in young healthy domestic cats is 16.7 ± 4.5 s. Tear BUT is positively correlated with STT values. Although mean tear film BUTs OD at 8–20 h following anesthesia were more rapid than preanesthesia values, this difference did not appear clinically relevant. [ABSTRACT FROM AUTHOR]

Mucins are secreted or transmembrane glycoproteins that are expressed mainly in the digestive tract. This family of proteins has been the focus of much gastric cancer research as some transmembrane mucins are implicated in tumorigenesis and make attractive targets for cancer diagnosis and therapeutics. Mucins have also been utilized to classify gastric cancer by differentiating between gastric and intestinal phenotypes. Here we show that transmembrane mucin MUC13 is upregulated in gastric cancer. By quantitative real-time reverse transcription-polymerase chain reaction and immunoblot analysis, overexpression of MUC13 was verified in more than half of the samples examined. In immunohistochemical analysis, MUC13 staining was observed in 74 of 114 cases of gastric cancer (64.9%), predominantly in intestinal type (P < 0.001), and in 9 of 10 cases of intestinal metaplasia, precancerous lesions of intestinal-type gastric cancer, but not observed in normal gastric mucosa. Moreover, MUC13 staining patterns characteristic of histological type were identified: staining was on the apical side of tubular glands in intestinal type and on the cytoplasm in diffuse type. These results suggest that MUC13 is a good differentiation marker for gastrointestinal mucosa and that it may have a causal role that correlates with two distinct gastric tumorigenesis pathways. (Cancer Sci2005; 96: 265 –274) [ABSTRACT FROM AUTHOR]

Caramori G, Di Gregorio C, Carlstedt I, Casolari P, Guzzinati I, Adcock I M, Barnes P J, Ciaccia A, Cavallesco G, Chung K F&Papi A(2004)Histopathology45,477–484Mucin expression in peripheral airways of patients with chronic obstructive pulmonary diseaseTo study the expression of mucins in peripheral airways in patients with chronic obstructive pulmonary disease (COPD).Peripheral lung sections from smokers with COPD (n = 9) and age-matched controls including smokers (n = 11) and lifelong non-smokers with normal lung function (n = 6) were stained with alcian blue, periodic acid–Schiff (PAS) and by immunohistochemistry of mucins (MUC): MUC2, MUC4, MUC5AC, MUC5B and MUC6. Histochemical staining and immunoreactivity of bronchiolar epithelium were graded and the presence or absence of stained mucus in the bronchiolar lumen was evaluated. There were no differences in alcian blue and PAS epithelial staining between the three groups. Intraluminal PAS staining was significantly more frequent among COPD subjects (P < 0.05). The expression of MUC5AC was significantly higher in the bronchiolar epithelium of patients with COPD (P < 0.05). Within the bronchiolar lumen, the predominant mucin was MUC5B. Intraluminal MUC5B was significantly more frequent among COPD patients (P < 0.05).COPD is specifically associated with increased expression of MUC5B in the bronchiolar lumen and of the mucin MUC5AC in the bronchiolar epithelium. These changes in mucin production in the peripheral airways may contribute to the pathophysiology of COPD. [ABSTRACT FROM AUTHOR]

In order to evaluate the significance of altered expression of mucin and cytokeratin during gallbladder carcinogenesis, we characteriazed the expressional profiles of MUC1, MUC2, MUC5AC, MUC6, CK7 and CK20 in 33 normal mucosa, 31 adenomas, 55 dysplasias and 131 carcinomas of the gallbladder. In normal gallbladder mucosa, the expressions of MUC5AC and MUC6 were diffuse and MUC1 expression was absent. However, in adenomas, dysplasias and carcinomas, the expressions of MUC5AC and MUC6 tended to decrease, whereas MUC1 expression was elevated. MUC2 and CK20 were infrequently expressed in all of the gallbladder epithelia, but adenomas expressing MUC2 and/or CK20 were more frequently associated with carcinomas and showed a higher grade of atypia than those without these antigens. In carcinomas, MUC1 expression was related to invasive growth, lymph node metastasis and a non-papillotubular type, whereas MUC6 expression was related to non-invasive growth. CK7 was diffusely expressed in almost all lesions, but carcinomas with a loss of CK7 expression showed poor survival. In conclusion, normal gallbladder mucosa has a gastric phenotype, but during carcinogenesis and tumor progression, the gastric phenotype is gradually lost and the aberrant expression of MUC1 occurs. The intestinal phenotype is not common in the gallbladder. [ABSTRACT FROM AUTHOR]

Myxoma is the most common benign neoplasm of the heart. This work is the first to present an unusual left atrium and mitral valve cardiac myxoma which cannot be completely resected. This cardiac myxoma was also associated with abundant mucopolysaccharidic matrix, including mucin. Mucin gene expression is cell- and tissue-specific, with variations during cell differentiation and inflammation, and is altered during carcinogenesis. The expression of mucin genes in cardiac myxoma has never been elucidated previously. Detailed immunohistochemical analysis of MUC1, MUC2 and MUC5AC has been performed in this left atrium and mitral valve myxoma. Notably, the expressions of mucins in cardiac myxoma must be further evaluated. [ABSTRACT FROM AUTHOR]

Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y & Yonezawa S (2004) Histopathology 44, 147–155 Combined status of MUC1 mucin and surfactant apoprotein A expression can predict the outcome of patients with small-size lung adenocarcinoma : Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Here, we aim to report a unique method to predict the recurrence and outcome of patients with pulmonary adenocarcinomas. : Immunohistochemical expression of MUC1 mucin and surfactant apoprotein A (SP-A) was examined in 185 cases of surgically removed lung adenocarcinomas of non-bronchioloalveolar type smaller than 30 mm. Staining results were evaluated semiquantitatively, and the expression of MUC1 and SP-A was compared in each case. There were 140/185 (76%) cases showing MUC1 expression higher than SP-A expression (MUC1>SP-A), and 45/185 (24%) cases showing MUC1 expression lower than or equal to SP-A expression (MUC1≤SP-A). Recurrence was observed in 24% (34/140) of the patients with a MUC1>SP-A pattern, but in 7% (3/45) of the patients with a MUC1≤SP-A pattern after the median observation period of 41 months (1–99 months) ( P < 0.01). The MUC1>SP-A group showed higher recurrence and worse survival than the MUC1≤SP-A group by Kaplan–Meier's method ( P < 0.01 and P < 0.005). Even in the patients with apparently favourable prognostic factors (well-differentiated adenocarcinoma or no lymph node metastasis), recurrence and survival were different between the two groups. : A high MUC1/SP-A ratio is strongly associated with a poor outcome in patients with small-size lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Mannweiler S, Beham A, Langner C. MUC1 and MUC2 expression in salivary gland tumors and in non-neoplastic salivary gland tissue. APMIS 2003;111:978–84. The expression of MUC1 and MUC2 was studied in salivary gland tumors and non-neoplastic salivary gland tissue. Formalin-fixed paraffin-embedded specimens from 101 patients (21 pleomorphic adenomas (PA), 22 Warthin's tumors (WT), 26 adenoid cystic carcinomas (ACC), 13 acinic cell adenocarcinomas (ACA), 9 mucoepidermoid carcinomas (MC), and 10 specimens of non-neoplastic parotid and submandibular gland tissue) were immunostained. All salivary gland tumors expressed MUC1. A strong immunoreactivity was noted in and , a moderate in and , and a weak in . Strong expression of MUC2 was noted in all , moderate expression in , and weak expression in and . All cases of except for two were negative for MUC2. In general, MUC1 expression was stronger than that of MUC2. Non-neoplastic salivary gland tissue revealed a moderate MUC1 and MUC2 expression in excretory ducts and a strong expression in striated ducts. The apical plasma membrane of some serous acini expressed MUC1. Mucous acini were negative for both antigens. No change in immunoreactivity was noted in cases of chronic sclerosing sialadenitis. In conclusion, the different expression pattern of MUC1 and MUC2 in salivary gland neoplasia may be of additional value for the classification of salivary gland tumors. [ABSTRACT FROM AUTHOR]

Helicobacter pylori shows a characteristic tropism for the mucus-producing gastric epithelium. In infected patients, H. pylori colocalizes in situ with the gastric secretory mucin MUC5AC. The carbohydrate blood-group antigen Lewis B (LeB) was deemed responsible for the adherence of H. pylori to the gastric surface epithelium. We sought to determine if MUC5AC is the carrier of LeB, and thus if MUC5AC is the underlying gene product functioning as the main receptor for H. pylori in the stomach. We studied three types of human tissue producing MUC5AC: Barrett's esophagus (BE), normal gastric tissue, and gastric metaplasia of the duodenum (GMD). Tissue sections were immuno-fluorescently stained for MUC5AC or LeB, and subsequently incubated with one of three strains of Texas red-labeled H. pylori, one of which was unable to bind to LeB. We determined the colocalization of MUC5AC or LeB with adherent H. pylori. The binding patterns for the two LeB-binding strains to all tissues were similar, whereas the strain unable to bind to LeB did not bind to any of the tissues. In normal gastric tissue, the LeB-binding strains always bound to MUC5AC- and LeB-positive epithelial cells. In four nonsecretor patients, colocalization of the LeB-binding strains was found to MUC5AC-positive gastric epithelial cells. In BE, the LeB-binding H. pylori strains colocalized very specifically to MUC5AC-positive cells. MUC5AC-producing cells in GMD contained LeB. Yet, LeB-binding H. pylori not only colocalized to MUC5AC or LeB present in GMD, but also bound to the LeB-positive brush border of normal duodenal epithelium. Mucin MUC5AC is the most important carrier of the LeB carbohydrate structure in normal gastric tissue and forms the major receptor for H. pylori. [ABSTRACT FROM AUTHOR]

Aims: Myxoglobulosis is a recognized variant of mucocele of the vermiform appendix. Myxoglobulosis has recently been reported in extravasation mucocele of the oral cavity. This morphological study was carried out to identify the prevalence and possible pathogenesis of this unusual feature. Materials and methods: A retrospective review of archival material diagnosed as oral cavity mucocele was undertaken. This covered a period of 32 months and consisted of 76 cases. In accordance with the proposed traumatic origin of extravasation mucocele, histological changes were classified on the basis of mucin extravasation and cyst formation. Globular structures, as described in the reports of myxoglobulosis, were looked for, as were changes that could be ascribed to their formation. Conclusions: Globular structures were noted in 22 (31%) of 71 cases of extravasation mucocele. They were present within cysts (11 samples) and in extraluminal connective tissue in the rest. They appeared to originate from alterations in connective tissue collagen following mucin extravasation. Their structure is different from that described in appendicial mucocele. When observed, they are best regarded as part of the normal sequence in the formation of oral cavity extravasation mucocele, without attaching special importance to them. [ABSTRACT FROM AUTHOR]

Aims: Adenocarcinomas of the distal oesophagus and especially the oesophago–gastric junction have shown an increasing incidence during the last decade. Definition of subgroups according to different sites of development, histogenesis or aetiology may prove to be valuable for clinical diagnosis and treatment. Previous studies have shown differences in cytokeratin patterns between Barrett's metaplasia of the oesophagus and intestinal metaplasia in the stomach. The aim of our study was to investigate whether the expression of certain cytokeratins (CK7, CK20) and mucins (MUC1, MUC2, MUC5AC) exhibit clear-cut patterns, thus allowing a subclassification of adenocarcinomas of the oesophago–gastric junction. The possibility of a relationship between antigen expression and the presence or absence of Barrett's metaplastic epithelium was also studied. Methods and results: CK7, CK20, MUC1, MUC2 and MUC5AC were visualized in six adenocarcinomas of the distal oesophagus, 29 adenocarcinomas of the oesophago–gastric junction and eight adenocarcinomas of the proximal stomach. CK7, CK20 and MUC1 were strongly expressed in the great majority of all neoplasms under study, whereas MUC2 and MUC5AC were absent or only faintly detectable. CK20 exhibited a significantly stronger expression in poorly differentiated tumours (G3) and MUC1 immunoreactivity correlated with tubular and papillary versus signet-ring cell histopathology. Other statistically significant correlations between antigens and histopathological features (pTNM stage, grading, histopathological subtype, presence/absence of Barrett's epithelium) were not observed. Conclusions: According to our results, most adenocarcinomas of the oesophago–gastric junction show a CK7+, CK20+, MUC1+ phenotype irrespective of the presence or absence of Barrett's epithelium. The immunohistochemical data suggest a similar histogenesis of these tumours. [ABSTRACT FROM AUTHOR]

Gene targeting often results in knockout mice that show several phenotypes, some of which may not directly relate to the intrinsic function of the disrupted gene. Hence, to sutdy the giological function of genesusing knockout mice, one must identify the defects that are directly due to the loss of the targeted gene. Runx3 is a transcription factor that regulates lineage-specific gene expression in developmental processes. Recently, two groups produced Runx3 knockout mice. two comparable defects were identified in both knockout strains, one involved neurogenesis and the other thymopoiesis. In addition, a stomach defect pertaining to gastric cancer was observed in one the mutant strains, but not in the other. Here, we assess the differences between the two Runx3 mutant strains and discuss further studies that could reconcile these discrepancies. This article highlights the difficulties of inferring gene function through the interpretation of knockout phenotypes. [ABSTRACT FROM AUTHOR]

Summary The purpose of the present study was to quantify the binding affinity between Tamm-Horsfall protein (THP) and complement 1q (C1q) using ELISA and a resonant mirror biosensor. In ELISA, immobilized THP was incubated with soluble C1q under both low and physiological ionic-strength conditions. Tamm-Horsfall protein bound C1q with an equilibrium dissociation constant (K D ) of 1.9 ± 0.6 nmol/L in low ionic-strength Tris buffers (20 mmol/L NaCl, pH 7.5) and with a lower affinity (K D of 13.4 ± 4.7 nmol/L) in physiological-strength Tris buffers (154 mmol/L NaCl, pH 7.5). A resonant mirror biosensor, which monitors binding events in real-time, was used to quantify the K D of this reaction, as well as to estimate the kinetic parameters. In these studies, THP and C1q bound with an association rate constant, k ass , of 1.25 × 10 5 L/mol per s and a dissociation rate constant, k diss , of 0.002–0.005/s. The calculated K D for the THP/C1q binding in low ionic-strength buffers was higher (averages of 10–15 nmol/L) than that obtained by the ELISA, while physiological ionic-strength buffers still reduced the affinity of this binding by an order of magnitude. In conclusion, THP consistently bound C1q with high affinity using several techniques. At least a portion of this interaction involved electrostatic events, as demonstrated by the influence of ionic strength on the binding affinity. [ABSTRACT FROM AUTHOR]

The lubrication properties of mucin and carboxymethylcellulose (CMC)-containing saliva substitutes and water were evaluated in a double-blind trial. After mouthrinsing with the substitutes, the patients answered a questionnaire (subjective effect) and the change of oral mucosal friction was measured with a probe (objective effect). Mucin and CMC-containing saliva substitutes showed almost the same objective effects, with changed friction values of about 15 min, which was more than twice as long as for water. Both water and the two saliva substitutes relieved the symptoms of dry mouth to some extent but they did not have a sufficiently long- lasting effect. [ABSTRACT FROM AUTHOR]

Salivary mucins can aggregate oral bacteria and are also constituents of pellicle and plaque. A, B, and H blood group antigens are present on the mucins of secretors only. These mucins have also been shown to contain more carbohydrate than non-secretor mucins. The aim of the present study was to relate these genetically determined differences in mucin composition to caries prevalence. Data on blood group, secretor status, and caries prevalence were collected from 69 dental students. In all blood groups, the average caries prevalence was lower for secretors than for non-secretors. The difference was more pronounced for smooth surface than for total surface prevalence. The secretors of blood group mucin A had the lowest caries prevalence. The results would be consistent with an impact of the mucin composition upon the caries prevalence, and possible mechanisms are discussed. [ABSTRACT FROM AUTHOR]

Reticular etythcmatous mucinosis is a rare syndrome which can be misdiagnosed as seborrhoeic dermatitis. This long-lasting skin disease, which is characterized by the histological presence of deposits of mucin in the dermis, usually responds to treatment with per os hydroxychloroquine, 400 mg/day, for 3 months. [ABSTRACT FROM AUTHOR]

The influence of mucin on the corrosion behaviour of seven typical dental casting alloys was investigated. A commercial saliva substitute (Saliva Orthana®) containing mucin, and a control from which the mucin had been removed, were used. The electrochemical behaviour of the test alloys was evaluated around the open circuit potential (OCP) utilizing standard potentiodynamic techniques, as a function of oxygen concentrations and pH. The results of the corrosion measurements were analysed by a four-way ANOVA to detect the influence of alloy, environment and possible interactions. Mucin seems to act as a cathodic inhibitor at pH 6.7 but not at pH 4.6. An unidentified component (e.g. benzoate) of the saliva substitute probably acts as an adsorption inhibitor. Anodic passivation is also correlated with the artificial saliva composition. [ABSTRACT FROM AUTHOR]

Studies into the electrochemical nature and corrosion behaviour of dental amalgam have indicated the need for an artificial saliva formula that will accurately simulate the electrochemical properties of natural saliva. Existing formulae have been based on inorganic saliva constituent concentrations, without accurate representation of organic constituents. Albumin and mucin were added to several dilutions of saline solution. The resulting solutions were used as electrolyte at 4° and 37°C for the potentiostatic anodic polarization of conventional amalgam. The presence of albumin and mucin did not appear to alter the major characteristics of corrosion profile. Examination of the current-time transient curves indicated, however, that the kinetics of the electrochemical reactions were delayed. Also, the open circuit potential was observed to shift to more active values with the addition of organic constituents, thereby creating a low current density region in the initial segment of the polarization profile. [ABSTRACT FROM AUTHOR]