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Biomedical subjects

David R Mack

Publications and source records attributed to David R Mack.

9 recordsLinked to original sources
PubMed2004

Role of probiotics in the modulation of intestinal infections and inflammation.

PURPOSE OF REVIEW: Using microorganisms to influence positively the course of an illness caused by injurious microorganisms is an approach with mounting clinical evidence showing efficacy. Whereas antibiotics will remain an important therapeutic option, there are limitations and problems to their increasing and chronic usage, and probiotics offer a strategy to reduce antibiotic usage. Increasingly, it has become clear that the mechanisms whereby probiotics can impact in intestinal diseases involve a large repertoire of responses. This review summarizes recent findings on how probiotics may effect benefit through interactions with host eukaryotic cells. RECENT FINDINGS: Limiting the access of microbes associated with the development of disease to host mucosal surfaces and altering the responses of host to microbial insults are potential mechanisms whereby probiotics can influence the pathogenesis of disease. Evidence is accumulating that live, viable probiotic organisms diminish accessibility to intestinal epithelial cell; however, the mucosal exclusion is not through direct blockage of shared epithelial receptors between probiotic microbes and pathogenic organisms. Modulation of mucosal defenses such as innate protective mechanisms, enhanced epithelial cell survival, and immune responses have all been shown to have potential in aiding in these actions. Intestinal epithelial cell adherence influences response and, as such, appears to be necessary but may not be wholly sufficient, because soluble bacterial factors have been reported to effect modulation of immune and nonimmune responses of eukaryotic cells. SUMMARY: There is a considerable repertoire of responses potentially responsible for the effects of probiotics, and these responses appear to involve a complex interplay between the microbes of the intestinal tract and the cells of the host. Continued work can be expected to further the understanding of the mechanisms involved, and more work is needed to determine the relative clinical importance of each of the phenomena. These studies are expected to help direct the most efficacious use of probiotics for inflammatory conditions arising from the intestinal tract.

Journal Article↗
PubMed2004

Probiotics in relapsing and chronic diarrhea.

Diarrhea is common in oncology patients; if it becomes chronic and relapsing, it can be debilitating, hinder planned management, and be difficult to treat. The authors describe two patients, one with leukemia who developed recurrent Clostridium difficile colitis and another who developed chronic diarrhea after bone marrow transplantation. In both patients, administration of antibiotics was suspected as the cause. In one patient, relapsing diarrhea resolved after probiotics were given with a 2-day course of metronidazole, and in the other patient, chronic diarrhea resolved after probiotics were given; resolution was maintained after the probiotics were stopped. Probiotics may offer a way to bring about resolution in antibiotic-associated chronic diarrhea.

Anti-Infective Agents↗
PubMed2004

D(-)-lactic acid-producing probiotics, D(-)-lactic acidosis and infants.

There is mounting evidence that ingestion of selected probiotics can modify disease morbidity for specific conditions affecting humans, and there is growing interest in the amelioration or prevention of disease with probiotics. Modulation in gene expression of the cellular elements of the intestinal mucosa and interbacterial interactions are leading theories as to the mechanism whereby probiotics can effect benefit for the host. Furthermore, gene-environmental interactions are considered to be important in the development of disease in those at genetic risk. With the intestinal tract harbouring large numbers of bacteria, alteration of the microbial environment with probiotic microbes is being considered as a controllable factor that may limit disease expression for those at genetic risk. This reasoning has led to interest in the administration of probiotics to infants. However, there are significant developmental changes occurring in many organ systems from the time of parturition and during the first months of life. Because there is little in the published scientific medical literature regarding the effects of long-term administration of probiotics to infants, potential problems must be considered; one such issue is that of administration of D(-)-lactate-producing probiotics. An appraisal of the current knowledge of this potential adverse effect is the subject of this communication.

Acidosis, Lactic↗
PubMed2003

Human serum amyloid A3 peptide enhances intestinal MUC3 expression and inhibits EPEC adherence.

We previously determined that the N-terminal region of bovine mammary-associated serum amyloid A3 (M-SAA3) increased intestinal mucin MUC3 levels in HT29 human intestinal cells by approximately 2.5-fold, relative to untreated cells. This study shows that the human M-SAA3 N-terminal peptide further enhances MUC3 transcript levels by approximately 4.3-fold in these cells (p<0.02), implicating a species-specific interaction. Furthermore, immunofluorescence and immunoblot analysis using a MUC3-specific monoclonal antibody confirms that the human M-SAA3 peptide stimulates MUC3 protein expression and secretion by the HT29 cells. More importantly, pretreatment of the cells with the peptide causes a subsequent 73% decrease in the adherence of enteropathogenic Escherichia coli (EPEC) to these cells, relative to untreated cells (p<0.01). The intestinal mucin MUC3 has been shown to provide a protective barrier in the gut and inhibit adherence of pathogens to the gut wall. Therefore, a means to increase MUC3 protein expression by a colostrum-associated peptide or protein may be a highly effective prophylactic treatment for the prevention of gastrointestinal diseases such as necrotizing enterocolitis and infectious diarrhea.

Amino Acid Sequence↗
PubMed2003

The conserved TFLK motif of mammary-associated serum amyloid A3 is responsible for up-regulation of intestinal MUC3 mucin expression in vitro.

In various mammalian species, an isoform of serum amyloid A is secreted at high concentrations into colostrum. A conserved four-amino-acid motif (TFLK) is contained within the first eight N-terminal amino acid residues of this mammary-associated serum amyloid A isoform 3 (M-SAA3). Peptides derived from the bovine N-terminal amino acid sequence of M-SAA3 were produced and added to cell culture medium of HT29 cells to study the effects on intestinal mucin gene expression. HT29 cells were grown to enhance expression of either MUC2 or MUC3 intestinal mucins. After incubation, total RNA was isolated for Northern blot analyses using MUC2 or MUC3 mucin cDNA probes. Signals were detected by autoradiography with mRNA levels expressed relative to 28S rRNA. The 10-mer peptides containing the intact TFLK-motif or a TFLK 4-mer peptide increased MUC3 mRNA expression compared with control cells (p < 0.05). There was no effect of these peptides on MUC2 mRNA expression. Cells that were incubated with 10-mer N-terminal derived peptides containing a scrambled TFLK motif, with all 10 amino acid residues scrambled or derived from a C-terminal region of M-SAA3, did not show increased MUC3 expression. Inhibition of enteropathogenic Escherichia coli strain E2348/69 adhesion to HT29 cells grown to enhance MUC3 expression was reduced by a similar amount when either peptides containing the intact TFLK motif or probiotic microbes were added to cell culture medium compared with control cells. M-SAA3 is a bioactive peptide secreted into colostrums that can up-regulate mucin expression and thereby may enhance innate protective mechanisms that limit access of deleterious microbes to intestinal mucosal epithelial cells in the postparturition period.

Amino Acid Motifs↗
PubMed2002

Peripheral blood intracellular cytokine analysis in children newly diagnosed with inflammatory bowel disease.

Patterns of cytokine profiles have emerged for different forms of inflammatory bowel disease with a predominance of type 1 cytokines in patients with Crohn disease and type 2 cytokine expression in patients with ulcerative colitis. Most of these studies have involved older patients with long-standing disease or after various therapeutic interventions, and patterns of cytokine expression were hypothesized to be influenced by these factors. To evaluate for these possibilities, we studied 23 patients (15 boys) with newly diagnosed Crohn disease (n = 14) or ulcerative colitis. Their mean age at diagnosis was 13.1 +/- 2.9 y (mean +/- SD). Healthy control subjects (n = 9) were previously obtained. Peripheral blood intracellular cytokine analysis was performed within 24 h using a modification of Becton Dickinson's FastImmune Cytokine system. Multiparametric flow cytometry and phenotyping of lymphocytes was performed. T-cell populations were defined as type 1 being CD69(+), CD3(+), and interferon-gamma(+) and type 2 being CD69(+), CD3(+), and IL-4(+). The median percent of type 1 T cells from normal subjects (2.8%) was similar to that of ulcerative colitis subjects (1.8%, p > 0.20) but greater than that of Crohn disease subjects (0.55%, p = 0.05). The median percent of type 2 lymphocytes in normal subjects (1.8%) was greater than that of ulcerative colitis subjects (0.35%, p = 0.02) but was similar to that of Crohn disease subjects (1.1%, p > 0.20). Serial determinations showed the median percent of type 2 T cells increased in ulcerative colitis patients as remission was induced. Reduced activated peripheral type 1 T cells of newly diagnosed, untreated children are similar to interferon-gamma expression in mucosa of adults with postoperative recurrence. Reduced type 2 cytokine expression patterns in subjects with ulcerative colitis are similar to lamina propria T-cell expression levels in adults and improve with disease remission.

Adolescent↗