Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.23 (beta-galactosidase)
14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intranasal administration of antigens coupled to full-length fibronectin-binding protein I (SfbI) of Streptococcus pyogenes results in the elicitation of improved humoral and cellular immune responses, at both systemic and mucosal levels. We want to evaluate if SfbI also exhibits adjuvant properties when co-administered with the antigen, as well as identify the minimal domain responsible for its adjuvanticity. To achieve this aim, mice were immunized by the intranasal route with the model antigen beta-galactosidase (beta-gal) co-administered with recombinant proteins spanning different portions of the SfbI protein. The obtained results demonstrated that the adjuvant properties of SfbI were maintained intact when admixed to the model antigen. Similar kinetics and absolute titers of beta-gal-specific IgG antibodies as well as a dominant IgG(1) isotype response pattern were observed using SfbI derivatives spanning either the aromatic and proline-rich (H10) or the fibronectin-binding (H12) domains, respectively. The use of all tested derivatives also stimulated the elicitation of efficient beta-gal-specific IgA responses in lung lavages (23-25% of the total IgA). The obtained results suggest that different sub-domains of the SfbI protein can be used as adjuvants for the development of mucosal vaccines.
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PMID:Identification of the domains of the fibronectin-binding protein I of Streptococcus pyogenes responsible for adjuvanticity. 1283 22

Chitin and chitosan derivatives are used as excipients and drug carriers in the pharmaceutical field. Their derivatization contributed to expansion of application and decrease toxicity. Chitosan is used as an excipient in oral dosage form. Chitosan tablet can exhibit a sustained drug release compared to commercial products. Films prepared using chitin or chitosan have been developed as wound dressings, oral mucoadhesive and water-resisting adhesive by virtue of their release characteristics and adhesion. Intratumoral administration of gadopentetic acid-chitosan complex nanoparticles (approximately 430 nm in diameter) has been more effective for gadolinium neutron-capture therapy compared with a group treated with the solution. Compared to intragastrical feeding with diphtheria toxoid (DT) in PBS, a strong enhancement of the systemic (IgG) and local (IgA) immune responses against DT has been observed in mice fed with DT loaded chitosan microparticles (approximately 4.7 microm in size). When DNA-loaded chitosan microspheres (1.15 - 1.28 microm) were intramuscularly administrated into mice, high beta-galactosidase and luciferase productions were obtained even after a long post-transfection period (12 weeks). N-Succinyl-chitosan (Suc-Chi) has been studied for cancer chemotherapy as a drug carrier and the conjugates of mitomycin C with Suc-Chi exhibited good antitumor activities against various tumors. Furthermore, trimethyl-chitosan and monocarboxymethyl-chitosan has been shown to be effective as intestinal absorption enhancers due to their physiological properties. Chitosan-thioglycolic acid conjugates has been found to be a promising candidate as scaffold material in tissue engineering due to their physicochemical properties. This review summarizes the application of chitin and chitosan derivatives for hospital preparations and drug carriers.
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PMID:Application of chitin and chitosan derivatives in the pharmaceutical field. 1452 20

Transferrin receptor (TfR) has been identified as a candidate IgA1 receptor expressed on human mesangial cells (HMC). TfR binds IgA1 but not IgA2, co-localizes with mesangial IgA1 deposits, and is overexpressed in patients with IgA nephropathy (IgAN). Here, structural requirements of IgA1 for its interaction with mesangial TfR were analyzed. Polymeric but not monomeric IgA1 interacted with TfR on cultured HMC and mediates internalization. IgA1 binding was significantly inhibited (>50%) by soluble forms of both TfR1 and TfR2, confirming that TfR serves as mesangial IgA1 receptor. Hypogalactosylated serum IgA1 from patients with IgAN bound TfR more efficiently than IgA1 from healthy individuals. Serum IgA immune complexes from patients with IgAN containing aberrantly glycosylated IgA1 bound more avidly to TfR than those from normal individuals. This binding was significantly inhibited by soluble TfR, highlighting the role of TfR in mesangial IgA1 deposition. For addressing the potential role of glycosylation sites in IgA1-TfR interaction, a variety of recombinant dimeric IgA1 molecules were used in binding studies on TfR with Daudi cells that express only TfR as IgA receptor. Deletion of either N- or O-linked glycosylation sites abrogated IgA1 binding to TfR, suggesting that sugars are essential for IgA1 binding. However, sialidase and beta-galactosidase treatment of IgA1 significantly enhanced IgA1/TfR interaction. These results indicate that aberrant glycosylation of IgA1 as well as immune complex formation constitute essential factors favoring mesangial TfR-IgA1 interaction as initial steps in IgAN pathogenesis.
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PMID:Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. 1497 64

HIV is transmitted sexually through mucosal surfaces where IgA Abs are the first line of immune defense. In this study, we used paired IgA and IgG mAbs against HIV gp160 to study intraepithelial cell neutralization and inhibition of HIV replication. African green monkey kidney cells, Vero C1008, polarizable epithelial cells transfected to express the polymeric Ig receptor (pIgR), were transfected with HIV proviral DNA, and intracellular neutralization mediated by the mAbs was assessed. D47A and D19A IgA, which neutralized HIV in a conventional assay, potently inhibited intracellular HIV replication as assessed by infecting HeLa-CD4-long terminal repeat/beta-galactosidase cells (human cervical carcinoma cell line) and CEMx174 cells (human T cell line) with apical supernatant, basolateral medium, and cell lysate from transfected cells. D47A also inhibited the production of virus as assessed by direct assay of p24. In contrast, D47 and D19 IgG, sharing the same V regions, but which were not transcytosed by the pIgR, did not inhibit intracellular HIV replication, nor did D47A and D19A IgA in pIgR- cells, incapable of transcytosing IgA. Confocal immunofluorescence microscopy showed prominent colocalization of HIV protein and D47A, in agreement with the intracellular neutralization data. D10A, which did not neutralize HIV in the conventional assay, and irrelevant IgA did not show intracellular neutralization or colocalization. Control studies with two kinds of conditioned medium confirmed that HIV neutralization had indeed occurred inside the cells. Thus, during its transcytosis through epithelial cells, HIV-specific IgA can neutralize HIV replication.
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PMID:Intraepithelial cell neutralization of HIV-1 replication by IgA. 1581 9

The development of mucosal adjuvants is still a critical need in vaccinology. In the present work, we show that bis(3',5')-cyclic dimeric GMP (cdiGMP), a second messenger that modulates cell surface properties of several microorganisms, exerts potent activity as a mucosal adjuvant. BALB/c mice were immunized intranasally with the model antigen beta-galactosidase (beta-Gal) coadministered with cdiGMP. Animals receiving cdiGMP as an adjuvant showed significantly higher anti-beta-Gal immunoglobulin G (IgG) titers in sera than controls (i.e., 512-fold [P < 0.05]). Coadministration of cdiGMP also stimulated efficient beta-Gal-specific secretory IgA production in the lung (P < 0.016) and vagina (P < 0.036). Cellular immune responses were observed in response to both the beta-Gal protein and a peptide encompassing its major histocompatibility complex class I-restricted epitope. The IgG1-to-IgG2a ratio of anti-beta-Gal antibodies and the observed profiles of secreted cytokines suggest that a dominant Th1 response pattern is promoted by mucosal coadministration of cdiGMP. Finally, the use of cdiGMP as a mucosal adjuvant also led to the stimulation of in vivo cytotoxic T-lymphocyte responses in C57BL/6 mice intranasally immunized with ovalbumin and cdiGMP (up to 30% of specific lysis). The results obtained indicate that cdiGMP is a promising tool for the development of mucosal vaccines.
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PMID:The bacterial second messenger cdiGMP exhibits promising activity as a mucosal adjuvant. 1756 66

The glycolipid alpha-galactosylceramide (alphaGalCer) has immunomodulatory properties, which have been exploited to combat cancer, chronic inflammatory diseases, and infections. However, its poor solubility makes alphaGalCer a suboptimal compound for in vivo applications. In this study, a pegylated derivative of alphaGalCer is characterized, which exhibits improved physical and biological properties. The new compound, alphaGalCerMPEG, is water-soluble and retains the specificity for the CD1d receptor of alphaGalCer. The in vitro stimulatory properties on immune cells (e.g., dendritic cells and splenocytes) are maintained intact, even when tested at a 33-fold lower concentration of the active moiety than alphaGalCer. NK cells isolated from mice treated with alphaGalCerMPEG also had stronger cytotoxic activity on YAC-1 cells than those obtained from animals receiving either alphaGalCer or CpG. Intranasal immunization studies performed in mice showed that alphaGalCerMPEG exerts stronger adjuvant activities than the parental compound alphaGalCer when tested at 0.35 vs 11.7 nM/dose. Coadministration of beta-galactosidase with alphaGalCerMPEG resulted not only in high titers of Ag-specific Abs in serum (i.e., 1:512,000), but also in the stimulation of stronger Th2 and secretory IgA responses, both at local and remote mucosal effector sites (i.e., nose, lung, and vagina). The new synthetic derivative alphaGalCerMPEG represents a promising tool for the development of immune interventions against infectious and noninfectious diseases.
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PMID:A pegylated derivative of alpha-galactosylceramide exhibits improved biological properties. 1767 64

Galactosialidosis is an autosomal recessive lysosomal disease associated with a deficiency of beta-galactosidase and neuraminidase. Described herein is the case of a young adult who had been diagnosed with galactosialidosis at 8 years of age. At the age of 30 years, proteinuria and hematuria appeared and the patient underwent a renal biopsy 1 year later. Light microscopy of the kidney sections indicated fine granular contents in the cytoplasm of glomerular endothelial and epithelial cells, arteriolar smooth muscles and proximal tubular epithelial cells on periodic acid silver-methenamin (PAM) stain. Electron microscopy of these cells indicated enlarged, smooth endoplasmic reticulum and lysosomes containing 150 nm-wide rods with a fine lattice structure at 66 A periodicity. Moreover, electron-dense deposits were located in the paramesangial area. Immunofluorescence staining indicated diffuse and global anti-human IgA and C3-positive staining as a mesangial pattern. Given these findings this patient was therefore diagnosed with both galactosialidosis and IgA nephropathy. This is the first report to describe light and electron microscopy observations of storage materials in the kidneys in young/adult galactosialidosis.
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PMID:Galactosialidosis associated with IgA nephropathy: morphological study of renal biopsy. 1842 28

Salmonella enteritidis infection has received attention during recent years owing to its high prevalence worldwide. In the present study, the protective effect of probiotic dahi (curd) supplemented with Lactobacillus acidophilus and L. casei against Salmonella enteritidis infection in mice is investigated. Seven days pre-feeding with probiotic dahi significantly increased anti-S. enteritidis sIgA (secretary IgA) antibodies and lymphocyte proliferation in S. enteritidis infected mice. IL-2, IL-6 and IFN-gamma production were significantly increased in supernatant of cultured splenocytes collected from mice pre-fed with probiotic dahi, while IL-4 levels were not changed significantly. Moreover, activities of beta-galactosidase and beta-glucuronidase, and counts of S. enteritidis in intestine, liver and spleen were decreased, whereas total lactobacilli in faeces were increased in mice pre-fed with probiotic dahi. Pre-feeding of probiotic dahi for 7 days was more effective than 2 days pre-feeding. Thus, the results indicate that, pre-feeding with probiotic dahi ameliorated S. enteritidis infection by stimulating specific and non-specific immune response. Above all, it lowered colonization of gastrointestinal tract as well as translocation of S. enteritidis.
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PMID:Dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei has a protective effect against Salmonella enteritidis infection in mice. 1914 89

In the present study, effect of dahi containing probiotic Lactobacillus casei (probiotic dahi) was evaluated to modulate immune response against Salmonella enteritidis infection in mice. Animals were fed with milk products along with standard diet for 2 and 7 days prior to the S. enteritidis challenge and continued on the respective dairy food-supplemented diets during the postchallenge period. Translocation of S. enteritidis in spleen and liver, beta-galactosidase and beta-glucuronidase enzymatic activities and secretory IgA (sIgA) in intestinal fluid, lymphocyte proliferation, and cytokine (interleukin [IL]-2, IL-4, IL-6, and interferon-gamma [IFN-gamma]) production in cultured splenocytes were assessed on day 2, 5, and 8 of the postchallenge period. Colonization of S. enteritidis in liver and spleen was remarkably low in probiotic dahi-fed mice than mice fed milk and control dahi. The beta-galactosidase and beta-glucuronidase activities in intestinal fluid collected from mice prefed for 7 days with probiotic dahi were significantly lower at day 5 and 8 postchallenge than in mice fed milk and control dahi. Levels of sIgA and lymphocyte proliferation rate were also significantly increased in probiotic dahi-fed mice compared with the other groups. Production of IL-2, IL-6, and IFN-gamma increased, whereas IL-4 decreased in splenic lymphocytes collected from probiotic dahi-fed mice. Data showed that dahi prefed for 7 days before S. enteritidis challenge was more effective than when mice were prefed for 2 days with dahi. Moreover, probiotic dahi was more efficacious in protecting against S. enteritidis infection by enhancing innate and adaptive immunity than fermented milk and normal dahi. Results of the present study suggest that prefeeding of probiotic dahi may strengthen the consumer's immune system and may protect infectious agents like S. enteritidis.
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PMID:Probiotic dahi containing Lactobacillus casei protects against Salmonella enteritidis infection and modulates immune response in mice. 1962 6

Here we demonstrated that bis-(3',5')-cyclic dimeric inosine monophosphate (c-di-IMP) exhibits potent adjuvant properties. BALB/c or C57BL/6 mice were immunized with the model antigens beta-galactosidase (beta-Gal) or Ovalbumin (OVA) alone or co-administered with c-di-IMP by the intranasal route. Animals receiving c-di-IMP showed significantly higher anti-beta-Gal or OVA immunoglobulin G titres (IgG) in sera than those vaccinated with beta-Gal or OVA alone. Furthermore, strong local immune responses were also detectable in different mucosal territories, as shown by the high levels of beta-Gal-specific secretory IgA (sIgA). The analysis of the antigen-specific IgG isotypes in sera, together with the profiles of the cytokines and chemokines secreted by lymphocytes from vaccinated animals showed that the use of c-di-IMP resulted in stimulation of a mixed T(H)1/T(H)2/T(H)17 response. Mucosal immunization of C57BL/6 mice with OVA using c-di-IMP as adjuvant also led to the stimulation of strong in vivo CTL responses (i.e., 60% of antigen-specific lysis) [corrected].Our results demonstrated that the novel compound c-di-IMP exhibits strong adjuvant properties when co-administered with an antigen by the mucosal route, thereby representing a promising candidate adjuvant for the development of mucosal vaccination strategies.
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PMID:The member of the cyclic di-nucleotide family bis-(3', 5')-cyclic dimeric inosine monophosphate exerts potent activity as mucosal adjuvant. 2006 May 10


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