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At least 1,081 records · Page 60Linked to original sources
PubMed2005

Immunostimulatory functions of membrane-bound and exported heat shock protein 70.

In the search for tumor-specific antigens, microbial and eukaryotic heat shock proteins (HSP) have been identified. Intracellularly, HSPs function as molecular chaperones supporting folding and transport of a great variety of polypeptides and proteins under normal physiological conditions and following stress stimuli. Furthermore, interferon-gamma and elevated body temperature induced by exercise have been found to increase serum levels of HSPs in humans. Extracellularly localized or plasma membrane-bound HSPs elicit a potent anti-cancer immune response mediated either by the adaptive or innate immune system. Following uptake of HSP (HSP70 and gp96)-peptide complexes by antigen presenting cells (APCs) and "cross-presentation" of HSP-chaperoned peptides on MHC class I molecules, a CD8-specific T cell response is induced. Apart from chaperoning tumor-specific peptides, HSPs per se provide activatory signals for the innate immune system. Binding of peptide-free HSP70 to APCs via Toll-like receptors (TLRs) initiates the secretion of pro-inflammatory cytokines and thus results in a broad non-specific immunostimulation. An unusual membrane localization of Hsp70, the major heat-inducible member of the HSP70 family, on tumor cells but not on corresponding normal tissues was found to act as a tumor-specific recognition structure for natural killer (NK) cells. Soluble as well as cell membrane-bound HSP70 can directly activate the cytolytic and migratory capacity of NK cells. APCs and tumor cells actively release HSP70s in lipid vesicles with biophysical properties of exosomes. These HSP70-presenting exosomes are thought to stimulate the adaptive and innate immune system in vivo. Taken together, depending on their intra/extracellular localization, peptide loading status, origin and route of application, HSPs either exert immune activation as danger signals in cancer immunity or protect cells from lethal damage induced by exogenous stress stimuli.

CD8-Positive T-Lymphocytes↗
PubMed2006

Probiotics as functional food in the treatment of diarrhea.

PURPOSE OF REVIEW: A disturbance in microbial balance of the gastrointestinal tract is often associated with diarrhea. Therefore, probiotics, as beneficial microorganisms for host health, have attracted clinical attention for their potential therapeutic application in the treatment of diarrhea. This review focuses on new research findings relevant to the effects of probiotics on diarrhea prevention and treatment and potential mechanisms of action for this alternative therapy for diarrhea. RECENT FINDINGS: Clinical trials suggest potential beneficial effects of probiotic therapy for preventing and treating antibiotic-associated diarrhea, acute diarrhea including rotavirus-induced diarrhea, traveler's diarrhea, and diarrhea-predominant irritable bowel syndrome. The most extensively studied probiotics for diarrhea are Lactobacillus, Bifidobacterium and Saccharomyces, with potential mechanisms of therapeutic action based on the protection of intestinal epithelial cell and barrier function, prevention of enterotoxin binding to intestinal epithelial cells, and regulation of intestinal microbial environment. SUMMARY: Growing evidence suggests that probiotics may serve as a functional food in the treatment of diarrhea. Remaining challenges include identifying mechanisms of action to provide the basis of more refined hypothesis-driven clinical trials. The correct combination and concentration of probiotics applied to the appropriate gastrointestinal disorders may improve the efficacy of this approach for diarrhea and other diseases.

Bifidobacterium↗
PubMed2002

Microbial-host interactions specifically control the glycosylation pattern in intestinal mouse mucosa.

The glycosylation of the intestinal cell layer is thought to control several key functions of the gut such as vectorial transports, defence against microbial agents or immunological processes. It has been assumed that the gut microflora may modulate the glycosylation pattern of the intestinal cell layer. However, there is no direct evidence for this regulatory process. The first goal of this work was to establish the germ-free mice intestinal glycosylation baseline using a histochemical approach and a panel of ten lectins with defined glycan specificities to tissue sections prepared from various cellular compartments of the small and large intestine. Using this baseline, we have studied the contribution of the gut microflora on the carbohydrate composition of glycoconjugates of intestinal cells by comparing the germ-free and conventional mice glycosylation patterns. Analysis of the germ-free mice intestinal glycosylation baseline revealed that the expression of glycans depends on the proximodistal gradient (small to large intestine) and on the cell lineage (absorptive, goblet, crypt, and Paneth cells), indicating that mice are able to create and maintain a strict topological and cell lineage-specific regulation of glycosyltransferase expression. By comparing germ-free and conventional mice, we find that the gut microflora specifically modulates the gut glycosylation pattern, quantitatively as well as qualitatively by changing the cellular and subcellular distribution of glycans. This is the first report in mice to directly demonstrate the critical contribution of microflora to intestinal glycosylation, a key characteristic of the gut.

Animals↗
PubMed1994

Microbial transformation of Ibuprofen by a nocardia species.

The carboxylic acid functional group of ibuprofen [alpha-methyl-4-(2-methylpropyl) benzene acetic acid] is reduced to the corresponding alcohol and subsequently esterified to the acetate derivative by cultures of Nocardia species strain NRRL 5646. The alcohol and ester microbial transformation products were isolated, and their structures were determined by H and C nuclear magnetic resonance spectroscopy and mass spectrometry. By derivatization of synthetic and microbiologically produced ibuprofen alcohols with S(+)-O-acetylmandelic acid, nuclear magnetic resonance analysis indicated that the carboxylic acid reductase of Nocardia sp. is R enantioselective, giving alcohol products with an enantiomeric excess of 61.2%. The R enantioselectivity of the carboxylic acid reductase enzyme system was confirmed by using cell extracts together with ATP and NADPH in the reduction of isomeric ibuprofens.

Journal Article↗
PubMed1995

Functional interaction of ligands and receptors of the hematopoietic superfamily in yeast.

Circulating peptide hormones and growth factors interact with cell surface receptors to initiate specific cellular responses. These complexes can consist of a simple association between two proteins or a more elaborate association of multiple proteins. We describe the functional expression of ligands and corresponding receptors in a microbial system useful for the rapid dissection of these important protein interactions. GH or PRL and extracellular domains of their respective receptors were functionally expressed as fusion proteins in an extended two-hybrid protein-protein interaction system. Reversible and specific ligand-receptor interactions were demonstrated by concurrent expression of free ligand peptides (GH or PRL) as binding competitors. The versatility established by expressing three heterologous proteins allowed for the investigation of higher order structures. Ligand-dependent GH receptor dimerization was demonstrated but PRL receptor dimerization was not observed in an analogous assay, suggesting that these related growth factors may not engage receptors in a similar manner. Additionally, significant association of GH receptors was observed in the absence of ligand, suggesting that there may be substantial avidity between these receptor proteins before ligand binding. Ligand-dependent and ligand-independent receptor dimerization was demonstrated by vascular endothelial growth factor and receptor proteins in similar assays. These findings indicate that extracellular protein interactions such as ligand-receptor association, as well as the formation of higher order protein structures important for the activation of hematopoietic receptors, can be rapidly investigated in this microbial expression system.

Binding, Competitive↗
PubMed2007

Ecological control analysis: being(s) in control of mass flux and metabolite concentrations in anaerobic degradation processes.

Identification of the functional groups of microorganisms that are predominantly in control of fluxes through, and concentrations in, microbial networks would benefit microbial ecology and environmental biotechnology: the properties of those controlling microorganisms could be studied or monitored specifically or their activity could be modulated in attempts to manipulate the behaviour of such networks. Herein we present ecological control analysis (ECA) as a versatile mathematical framework that allows for the quantification of the control of each functional group in a microbial network on its process rates and concentrations of intermediates. In contrast to current views, we show that rates of flow of matter are not always limited by a single functional group; rather flux control can be distributed over several groups. Also, control over intermediate concentrations is always shared. Because of indirect interactions, through other functional groups, the concentration of an intermediate can also be controlled by functional groups not producing or consuming it. Ecological control analysis is illustrated by a case study on the anaerobic degradation of organic matter, using experimental data obtained from the literature. During anaerobic degradation, fermenting microorganisms interact with terminal electron-accepting microorganisms (e.g. halorespirers, methanogens). The analysis indicates that flux control mainly resides with fermenting microorganisms, but can shift to the terminal electron-accepting microorganisms under less favourable redox conditions. Paradoxically, halorespiring microorganisms do not control the rate of perchloroethylene and trichloroethylene degradation even though they catalyse those processes themselves.

Bacteria, Anaerobic↗
PubMed2000

Micronutrients and infection: interactions and implications with enteric and other infections and future priorities.

Symposium presentations have focused on the elegant molecular science and the biologic mechanisms by which micronutrients play critical roles in cellular and humoral immune responses, cellular signaling and function, and even in the evolution of microbial virulence. The concluding session examined the practical issues of how best to evaluate the nutritionally at-risk host, especially in the areas of greatest need-an analytical model of nutrient-immune interactions, implications of nutritional modulation of the immune response for disease, and the implications for international research and child health. This overview illustrated how malnutrition may be a major consequence of early childhood diarrhea and enteric infections, as enteric infections may critically impair intestinal absorptive function with potential long-term consequences for growth and development. The potentially huge, largely undefined DALY (disability-adjusted life years) impact of early childhood diarrheal illnesses demonstrates the importance of quantifying the long-term functional impact of largely preventable nutritional and infectious diseases, especially in children in developing areas.

Child↗
PubMed2025

Dual-approach analysis of gut microbiome in patients with type 1 diabetes and diabetic kidney disease.

BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disease mediated by genetic, epigenetic, and environmental factors. Diabetic kidney disease (DKD) is a major complication of diabetes mellitus which affects 30-40% of T1D patients. Increasing evidence suggests the significant role of the microbiome in the progression of both T1D and DKD. MATERIALS AND METHODS: Here we recruited 76 T1D patients and 22 healthy controls and combined data from sigmoid colon biopsy samples analysed with V3-V4 region amplification of 16S rRNA gene and shotgun metagenomics data obtained from faecal samples. Additionally, we compared T1D patients with and without progression of DKD. RESULTS: We observed significant differences within both sample types at various taxonomic and functional levels. T1D patient microbiota detected using biopsy samples had a lower abundance of the Bacteroides genus when compared to healthy controls. Significantly, despite only a few taxonomic differences patients with and without DKD progression were vastly different at the functional pathway level within the faecal samples - we observed 2 and 61 enriched pathways in these groups. respectively, with several of these pathways linked to the mediation of renal function. CONCLUSION: Altogether, we present novel data about microbial signatures relevant to T1D and DKD progression, which partly supports previous data and also presents possible tissue type or population-specific elements. DKD progression is characterized with significant differences within the functional level of the gut microbiome.

Humans↗
PubMed1995

Influence of a pre-operative enteral supplement on functional activities of peripheral leukocytes from patients with major surgery.

Following severe trauma or major surgery patients develop functional alterations of host defense mechanisms which contribute an enhanced susceptibility towards microbial infections. Several studies have demonstrated that a specialized nutritional regimen may improve immune functions. We analyzed leukocyte functions from 40 patients undergoing major upper gastrointestinal surgery in a randomized placebo-controlled double-blind study. Patients were divided into two groups, one received 5 days pre-operatively an orally given experimental supplement enriched with omega-3-fatty acids, arginine, and ribonucleic acid (RNA), the other an isocaloric, control supplement. The experimental group generated significantly more leukotriene B(5) (LTB(5)) as compared to the control group. In contrast, the capacity to generate leukotriene B(4) (LTB(4)) as well as the synthesis of interleukin-8 (IL-8) was not significantly different in both groups. Additionally, lymphocyte/monocyte proliferation was analyzed and donor specific heterogeneities were observed; but no significant differences were found between the two nutritional regimens.

Journal Article↗
PubMed2003

Airway inflammation in waste handlers exposed to bioaerosols assessed by induced sputum.

Work-associated lower airway inflammation in waste collectors was examined by induced sputum and correlated with the bioaerosol exposure. Organic waste collectors (n=25) underwent induced sputum collection and spirometry before work on Monday and the following Thursday. Total cells, cell differentials, interleukin (IL)-8 and eosinophilic cationic protein were determined. Personal full-shift exposure measurements were performed Monday, Tuesday and Wednesday and analysed for total bacteria, fungal spores, endotoxins and beta(1-3)-glucans. The percentage of neutrophils (46-58%) and the IL-8 concentration (1.1-1.4 ng x mL(-1)) increased from Monday to Thursday. Forced expiratory volume in one second (FEV1) was significantly reduced on Thursday, and the decrease in FEV1/forced vital capacity correlated with the increase in the percentage of neutrophils. The median exposure to endotoxin (range 7-180 EU x m(-3)) and beta(1-3)-glucan (range 5-220 ng x m(-3)) was correlated with the increase in IL-8. Bioaerosol exposure during waste collection induced an inflammatory response in the lower airways, characterised by neutrophils and interleukin-8 secretion, that influenced the lung function. The inflammatory response was related to microbial components in the bioaerosol and was more pronounced for endotoxin than beta(1-3)-glucan exposure. No associations were found for mould spores or bacteria.

Aerosols↗
PubMed1997

Short-chain fatty acid-initiated cell cycle arrest and apoptosis of colonic epithelial cells is linked to mitochondrial function.

Butyrate, a short-chain fatty acid produced during microbial fermentation of fiber, induces growth arrest, differentiation, and apoptosis of colonic epithelial cells in vitro, and our prior work has shown that this induction is tightly linked to mitochondrial activity. Here we demonstrate that 12 h following induction, SW620 human colonic carcinoma cells accumulate simultaneously in G0-G1 and G2-M of the cell cycle. Four h later, during this G0-G1 to G2-M arrest, cells begin to undergo apoptosis. Using a series of unrelated agents that modulate mitochondrial functions, we demonstrate that mitochondrial electron transport and membrane potential are critical in initiation of this butyrate-mediated growth arrest and apoptosis. Colonic tumorigenesis is characterized by abnormalities in proliferation, apoptosis, and mitochondrial activities. Thus, butyrate may reduce risk for colon cancer by inducing a pathway that enhances mitochondrial function, ultimately resulting in initiation of growth arrest and apoptosis of colonic epithelial cells.

Apoptosis↗
PubMed2002

The highest priority: what microbial genomes are telling us about immunity.

Study of microbial genomes has provided new insight into the functions that pathogens require for survival in the animal host. Small genome bacterial pathogens, defined as those < or = 1/3 the size of Escherichia coli, include chlamydiae, rickettsiae and ehrlichiae, mycoplasmas, and spirochetes. The small genome size is believed to result from reductive evolution, a process of initial mutation with loss of function followed by progressive accumulation of mutations and eventual gene deletion. This is most notable in the 1.1 Mb genome of Rickettsia prowazekki in which 24% of the genome is non-coding, as compared to approximately 10% in the 4.4 Mb E. coli. Consequently, these pathogens are thus presumed to retain only the most important functions for survival and propagation. There is consistent evidence from small genomes that the genetic deletion is primarily related to the loss of metabolic function and especially reduction of multiple overlapping pathways and duplicated genes. Thus, these pathogens undergo progressive reduction in their genomes yet maintain the ability to infect, survive within, and cause disease in animals. In the face of this reductive process, what genes and associated functions are maintained? Strikingly, these pathogens devote a high percentage of their genomes to paralogous families of polymorphic surface molecules. This retention suggests that evasion of the immune response is the highest priority of obligate microbial pathogens and provides a strategy for identifying protective antigens for vaccine development to control disease.

Adaptation, Physiological↗
PubMed1996

Rapid increase in inducible nitric oxide synthase gene expression in the heart during endotoxemia.

Inducible, Ca(2+)-independent nitric oxide (NO) synthase activity in the heart is elevated during endotoxemia and the resulting excess release of NO depresses cardiac contractile function. We show here that this is due to an extremely rapid induction of inducible NO synthase gene expression. Following injection of endotoxin (bacterial lipopolysaccharide) in rats we detected increased inducible NO synthase mRNA levels in the left ventricular wall within 30 min which then peaked at 3 h. This was followed by an increase in myocardial inducible NO synthase enzyme activity and plasma levels of NO metabolites, nitrate and nitrite, which peaked at 6 and 12 h, respectively. The extremely rapid induction of inducible NO synthase may serve to protect the heart against microbial infection and concomitantly alter myocardial mechanical function.

Animals↗
PubMed1996

Effectiveness of Natuphos phytase in improving the bioavailabilities of phosphorus and other nutrients in soybean meal-based semipurified diets for young pigs.

Crossbred pigs (n = 96, BW = 7.5 kg) were used in a 5-wk trial to determine the effectiveness of supplemental Natuphos phytase in improving the bioavailabilities of P and other nutrients in a semipurified diet with soybean meal as the only P source in the basal diet. Two available P (aP) levels (.05 and .16%) and five phytase levels (0, 350, 700, 1,050, and 1,400 units/kg of diet) were used in a 2 x 5 factorial arrangement of treatments. In addition to the 10 diets, two extra diets were formulated to supply the recommended level of aP (.32%) with 0 and 1,400 units (U) of phytase/kg of diet. Graded levels of phytase resulted in linear increases in ADG (P < .02), ADFI (P < .01 at .16% aP only), and gain:feed ratio (P < .03). Effects of adding phytase to the diet with .32% aP were observed only in the first 14 d of the study with increases in ADG (P < .06) and gain:feed (P < .02) for added phytase. Apparent digestibility (or absorption) coefficients (ADC) of DM, P, Ca, and N were estimated using chromic oxide as an indicator during wk 4 and 5. When phytase and P were added to the low P diet, the ADC of P was increased (P < .01), but only small and variable changes in the ADC of DM, Ca, and N were observed. Fecal P excretion (grams per day) decreased as microbial phytase was added (P < .01) and increased with added P (P < .01). In comparison to the results with the .32% aP diet, fecal P excretion decreased 25 to 50% by the addition of phytase. The addition of phytase to the diet with .32% aP further improved (P < .01) the ADC of P (54.5 vs 61.8%) and decreased (P < .01) fecal P excretion (1.62 vs 1.38 g/d). Characteristics of 4th metacarpals and 10th ribs were consistently improved by increasing dietary levels of both phytase and P. On the basis of an assessment of R2 values from secondorder translog equations, ADG, ADFI, P apparent absorption, bone ash percentage, and bone shear force were sensitive indicators to evaluate phytase efficacy of P availability in diets. Phosphorus equivalency of microbial phytase was calculated by using response equations for ADG and apparent P absorption. The average function of the release of P (Y, grams per kilograms) by microbial phytase (X, units per kilogram of diet) was developed with aP levels of .05 and .16%: Y = 1.546-1.504e-.0015X. The replacement of 1 g of inorganic P would require about 676 U of microbial phytase. This represents 77% of released P from phytate.

6-Phytase↗
PubMed2005

Fishing for biodiversity: novel methanopterin-linked C transfer genes deduced from the Sargasso Sea metagenome.

The recently generated database of microbial genes from an oligotrophic environment populated by a calculated 1800 major phylotypes (the Sargasso Sea metagenome-SSM) presents a great source for expanding local databases of genes indicative of a specific function. In this article we analyse the SSM for the presence of methanopterin-linked C1 transfer genes that are signature for methylotrophy. We conclude that more than 10 phylotypes possessing genes of interest are present in this environment. The sequences representative of these major phylotypes do not appear to belong to any known microbial group capable of methanopterin-linked C1 transfer. Instead, these sequences separate from all known sequences on phylogenetic trees, pointing toward their affiliation with novel microbial phyla. These data imply a broader distribution of methanopterin-linked functions in the microbial world than has been previously known.

Biodiversity↗
PubMed1983

Pyoderma eczema and folliculitis with defective leucocyte and lymphocyte function: a new familial immunodeficiency disease responsive to a histamine-1 antagonist.

A new familial immunodeficiency disease characterised by recurrent and persistent pyoderma, folliculitis, and atopic dermatitis is described in a father and son. It is accompanied by abnormalities of lymphocyte function (including defective proliferative responses to phytomitogens, and subnormal response in immunoglobulin production after stimulation of the lymphocytes by pokeweed mitogen) and defective leucocyte chemiluminescence responses, which were associated with defective ability for intracellular killing of microbial organisms. The abnormalities of lymphocyte and leucocyte function, as well as the clinical manifestations, responded dramatically to treatment with the histamine-1 antagonist, chlorpheniramine, suggesting that the underlying defect in this disease may relate to defective histamine metabolism or abnormal expression of histamine receptors on lymphocytes and leucocytes.

Blepharitis↗
PubMed2000

Unaltered phenotype, tissue distribution and function of Valpha14(+) NKT cells in germ-free mice.

The expression pattern of mouse CD1d and the tissue distribution of CD1d-restricted Valpha14-Jalpha281 NKT cells suggest that the liver and the marginal zone of the spleen might be preferred sites of activation of this potent innate pathway of early cytokine secretion. Because these tissues are particularly involved with the filtration of blood-borne pathogens, and because NKT cells with an activated / memory phenotype accumulate over the first weeks of life and their CD1 ligands bind microbial glycolipids, it has been hypothesized that expansion of the NKT cell subset may be driven by exposure to the microbial environment. To test this hypothesis, we analyzed the frequency, surface phenotype and functional properties of NKT cells in normal and in germ-free C57BL / 6 mice. Surprisingly, we found that the NKT cell subset develops in the presence or absence of a microbial environment. Although these results do not rule out the possibility that NKT cells exert a protective function against some microbial agents, they demonstrate that non microbial ligands, possibly self-antigens are sufficient for the generation, maturation and peripheral accumulation of NKT cells.

Animals↗