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Biomedical subjects

J Van de Water

Publications and source records attributed to J Van de Water.

At least 19 recordsLinked to original sources
PubMed2006

Fatty acid compositions of red blood cell phospholipids in children with autism.

We compared the compositions of fatty acids including n-3, n-6 polyunsaturated fatty acids, trans- and cis-monounsaturated fatty acids, and saturated fatty acids in the red blood cell membranes of 40 children with autism (20 with early onset autism and 20 with developmental regression) and age-matched, 20 typically developing controls and 20 subjects with non-autistic developmental disabilities. The main findings include increased levels of eicosenoic acid (20:1n9) and erucic acid (22:1n9) in autistic subjects with developmental regression when compared with typically developing controls. In addition, an increase in 20:2n6 and a decrease in 16:1n7t were observed in children with clinical regression compared to those with early onset autism. Our results do not provide strong evidence for the hypothesis that abnormal fatty acid metabolism plays a role in the pathogenesis of autism spectrum disorder, although they suggest some metabolic or dietary abnormalities in the regressive form of autism.

Autistic Disorder↗
PubMed2005

Effects of a Spirulina-based dietary supplement on cytokine production from allergic rhinitis patients.

Spirulina represents a blue-green alga that is widely produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. We have previously shown that the in vitro culture of Spirulina with human peripheral blood mononuclear cells (PBMCs) modulated the production of cytokines. In the present study, we evaluated the impact of a Spirulina-based dietary supplement (Earthrise Nutritionals, Inc., Irvine, CA) on patients with allergic rhinitis by assessing the production of cytokines [interleukin (IL)-4, interferon (IFN)-gamma, and IL-2] critical in regulating immunoglobulin E-mediated allergy. In a randomized double-blinded crossover study versus placebo, allergic individuals were fed daily with either placebo or Spirulina, at 1,000 mg or 2,000 mg, for 12 weeks. PBMCs isolated before and after the Spirulina feeding were stimulated with phytohemagglutinin (PHA) prior to determining the levels of cytokine from cell culture supernatants. Although Spirulina seemed to be ineffective at modulating the secretion of Th1 cytokines (IFN-gamma and IL-2), we discovered that Spirulina, administered at 2,000 mg/day, significantly reduced IL-4 levels by 32% from PHA-stimulated cells. These results indicate that Spirulina can modulate the Th profile in patients with allergic rhinitis by suppressing the differentiation of Th2 cells mediated, in part, by inhibiting the production of IL-4. To our knowledge, this is the first human feeding study that demonstrates the protective effects of Spirulina towards allergic rhinitis.

Adolescent↗
PubMed2002

Effect of cocoa flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells.

We previously showed that flavanols and their related oligomers (FLO) isolated from cocoa can have immunomodulatory effects on production of the cytokines interleukin-1beta (IL-1beta), IL-2, and IL-4. In the present study, we examined whether selected FLO fractions isolated from cocoa (monomer through decamer) modulate IL-5 protein secretion from resting and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). Although FLO fractions were unstimulatory for IL-5 secretion in resting cells, PHA-induced IL-5 release from PBMC was markedly affected by certain FLO fractions. The monomeric and small oligomeric (dimer and trimer) fractions enhanced PHA stimulation by 50%, 54%, and 43%, respectively. In contrast, the larger oligomeric fractions (hexamer through decamer) inhibited IL-5 release in the range of 18% to 39%; the tetramer and pentamer showed intermediate effects. The increment in IL-5 suggests that FLO may preferentially stimulate immunoglobulin A. We suggest that in the oral cavity this could result in reduction in the risk for dental caries and periodontal disease. This work offers additional data for consideration of the health benefits of dietary FLO from a variety of foods, including those benefits associated specifically with consumption of some cocoas and chocolates.

Antioxidants↗
PubMed2001

Immunoreactivity of organic mimeotopes of the E2 component of pyruvate dehydrogenase: connecting xenobiotics with primary biliary cirrhosis.

In primary biliary cirrhosis (PBC), the major autoepitope recognized by both T and B cells is the inner lipoyl domain of the E2 component of pyruvate dehydrogenase. To address the hypothesis that PBC is induced by xenobiotic exposure, we took advantage of ab initio quantum chemistry and synthesized the inner lipoyl domain of E2 component of pyruvate dehydrogenase, replacing the lipoic acid moiety with synthetic structures designed to mimic a xenobiotically modified lipoyl hapten, and we quantitated the reactivity of these structures with sera from PBC patients. Interestingly, antimitochondrial Abs from all seropositive patients with PBC, but no controls, reacted against 3 of the 18 organic modified autoepitopes significantly better than to the native domain. By structural analysis, the features that correlated with autoantibody binding included synthetic domain peptides with a halide or methyl halide in the meta or para position containing no strong hydrogen bond accepting groups on the phenyl ring of the lysine substituents, and synthetic domain peptides with a relatively low rotation barrier about the linkage bond. Many chemicals including pharmaceuticals and household detergents have the potential to form such halogenated derivatives as metabolites. These data reflect the first time that an organic compound has been shown to serve as a mimeotope for an autoantigen and further provide evidence for a potential mechanism by which environmental organic compounds may cause PBC.

Amino Acid Sequence↗
PubMed2001

Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: the molecule versus the mimic.

The 2-oxo-acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC-E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC-E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC-E2 or a cross-reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC-E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide-on-bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC-E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC-E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC-E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC-E2.

Amino Acid Sequence↗
PubMed2000

The effect of cocoa procyanidins on the transcription and secretion of interleukin 1 beta in peripheral blood mononuclear cells.

Recent data has demonstrated that cacao liquor polyphenols (procyanidins) have antioxidant activity, inhibit mRNA expression of interleukin-2 and are potent inhibitors of acute inflammation. Given the widespread ingestion of cocoa in many cultures, we investigated whether cocoa, in its isolated procyanidin fractions (monomer through decamer), would modulate synthesis of the pro-inflammatory cytokine, interleukin-1 beta. Both resting and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) were investigated at the levels of transcription and protein secretion. Individual cocoa fractions were shown to augment constitutive IL-1 beta gene expression, although values varied between subjects. Interestingly, the smaller fractions of cocoa (monomer-tetramer) consistently reduced IL-1 beta expression of PHA-stimulated cells by 1-15%, while the larger oligomers (pentamer-decamer) increased expression by 4-52%. These data, observed at the transcription level, were reflected in protein levels in PHA-induced PBMC. The presence or absence of PHA did not alter the effects of the cocoa procyanidins with the exception of the pentamer. This study offers additional data for the consideration of the health-benefits of dietary polyphenols from a wide variety of foods, including those benefits associated specifically with cocoa and chocolate consumption.

Antioxidants↗
PubMed1999

Autoepitope mapping and reactivity of autoantibodies to the dihydrolipoamide dehydrogenase-binding protein (E3BP) and the glycine cleavage proteins in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial antibodies (AMA) directed primarily against the E2 subunits of the pyruvate dehydrogenase complex, the branched chain 2-oxo-acid dehydrogenase complex, the 2-oxoglutarate dehydrogenase complex, as well as the dihydrolipoamide dehydrogenase-binding protein (E3BP) of pyruvate dehydrogenase complex. The autoantibody response to each E2 subunit is directed to the lipoic acid binding domain. However, hitherto, the epitope recognized by autoantibodies to E3BP has not been mapped. In this study, we have taken advantage of the recently available full-length human E3BP complementary DNA (cDNA) to map this epitope. In addition, another lipoic binding protein, the H-protein of the glycine cleavage complex, was also studied as a potential autoantigen recognized by AMA. Firstly, the sequence corresponding to the lipoic domain of E3BP (E3BP-LD) was amplified by polymerase chain reaction and recombinant protein and then purified. Immunoreactivity of 45 PBC sera (and 52 control sera) against the purified recombinant E3BP-LD was analyzed by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Secondly, reactivity of PBC sera was similarly analyzed by immunoblotting against H-protein. It is interesting that preabsorption of patient sera with the lipoic acid binding domain of E3BP completely removed all reactivity with the entire protein by immunoblotting analysis, suggesting that autoantibodies to E3BP are directed solely to its lipoic acid binding domain. Fifty-three percent of PBC sera reacted with E3BP-LD, with the majority of the response being of the immunoglobulin G (IgG) isotype (95%). Surprisingly, there was little IgM response to the E3BP-LD suggesting that the immune response was secondary because of determinant spreading. In contrast, H-protein does not appear to possess (or expose) autoepitopes recognized by PBC sera. This observation is consistent with structural data on this moiety.

Amino Acid Oxidoreductases↗
PubMed1999

Generation of monoclonal antibodies to murine bile duct epithelial cells: identification of annexin V as a new marker of small intrahepatic bile ducts.

Biliary epithelial cells (BECs) are distributed along the length of both the extrahepatic and intrahepatic biliary tree, but have distinctly different phenotypes and functions according to their anatomical location. It has been reasoned that the distinct appearance of pathogenic lesions in different biliary diseases may be associated with the expression of distinct proteins. These data prompted us to immunize rats with cultured murine BECs with the objective of determining if there are unique antigens on BECs. Of the 45 monoclonal antibodies (mAbs) produced, 12 mAbs (MBEC 1-12) were selected for detailed study based on their classification into three major groups. These groups included four antibodies (MBEC 1-4) that reacted in a staining pattern typical of mucin. A second group of mAbs, MBECs 5 to 8, reacted strongly along the biliary tract and by immunoblot analysis, reacted with several bands ranging from 44 kd to 64 kd. These antibodies were considered as markers of pan BECs and their staining pattern proved similar to that of a control polyclonal pan-cytokeratin. The final group of mAbs, MBECs 9 to 12, recognized a 36-kd antigen using lysates of murine BECs. These antibodies also predominantly stained small peripheral bile ducts. The reactive antigen was purified by immunoprecipitation and microsequenced; the peptides sequenced showed 100% homology with murine annexin V. The identification of annexin V with predominantly intrahepatic bile ducts, is of significant interest because of the multiple roles of annexin V, including that of membrane cytoskeletal interactions during transport and apoptosis.

Amino Acid Sequence↗
PubMed1999

Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation.

Primary biliary cirrhosis (PBC) and graft-versus-host disease (GVHD) are thought to have common immunopathologic features and previous studies have reported that 5.2 to 81% of patients with chronic GVHD after allogeneic hematopoietic cell transplant have antimitochondrial antibodies (AMA). We studied a total of 89 patients with chronic GVHD and 60 controls for AMA reactivity by ELISA and immunoblotting using recombinant PDC-E2, BCOADC-E2, and OGDC-E2, immunoblotting of beef heart mitochondrial proteins, and reactivity to nuclei, smooth muscle (ASMA), ribonucleoprotein JO-1, extractable nuclear antigen, nuclear proteins SSA/ SSB, ribonucleic P proteinase III, cardiolipin (ACA), liver kidney microsomal, thyroid microsomal, myeloperoxidase, and the reactivity of rheumatoid factor. A subset of 60 chronic GVHD sera were tested for reactivity to gp210 and LBR. Finally, liver tissue from patients with chronic GVHD and PBC was studied by immunohistochemistry to determine whether there was comparable abnormal apical staining of biliary epithelial cells using PDC-E2-specific monoclonal antibodies. Surprisingly, there were no AMA found in the sera from the 89 patients with chronic GVHD. Review of published data on AMA in GVHD suggests that previous results were primarily false positives. In contrast, sera from the patients with GVHD did have a variety of other autoantibodies and, in particular, 20/89 (22.4%) positive ANA, 23/89 (25.8%) positive ASMA, and 9/89 (10.1%) positive ACA. The other autoantibodies assayed were not statistically different from controls. Finally, abnormal biliary epithelial luminal staining of bile ducts was found, as expected, in liver tissue of patients with PBC but was absent in chronic GVHD.

Adult↗
PubMed1999

The influence of chronic yogurt consumption on immunity.

There has been increased interest in the study of nutrition and immunity. This is especially true with respect to the hypothesis that consumption of specific foods may reduce an individual's susceptibility to the establishment and/or progression of immunologic disease. Although an increased intake of a specific food may improve health status in select cases, chronic consumption of large amounts of one specific food may in fact be detrimental. The studies described here examined the long-term effect of yogurt consumption on two different age populations, young adults (20-40 y) and senior adults (55-70 y). There were three study groups per age group, live-culture yogurt, pasteurized yogurt and control (no yogurt), given 200 g/d of yogurt for 1 y. The subjects completed a questionnaire detailing health parameters on a weekly basis and a 4-d food record was taken monthly. Blood was taken every 3 mo and complete blood chemistry, blood count, total and specific immunoglobulin (Ig)E, and interferon-gamma (IFN-gamma) production measured. Yogurt consumption, especially for the live-culture groups, was associated with a decrease in allergic symptoms in both age groups. Seniors in the control group experienced an increase in both total and LDL cholesterol, whereas those in the yogurt groups remained stable during the course of the study. There was little effect on IFN-gamma and IgE production, although seniors in the yogurt group had lower levels of total IgE throughout the year.

Adult↗
PubMed1999

Is there a serological difference between men and women with primary biliary cirrhosis?

OBJECTIVE: Primary biliary cirrhosis (PBC) is an autoimmune disease affecting small intrahepatic bile ducts of the liver, causing destruction of the epithelium that results in eventual fibrosis and scarring. We still lack a complete epidemiological description of this disease, although interesting geographic differences in prevalence have been described. One consistent feature has been the relative scarcity of men with PBC. In fact, published ratios of women to men range from 3:1 to as high as 22:1. Thus far, the only clinical difference reported between men and women with PBC is a putative higher risk of hepatocarcinoma in men. Previous serological studies have shown that about 95% of all patients possess antimitochondrial antibodies to members of the highly conserved 2-oxo-acid dehydrogenase family of proteins, namely pyruvate dehydrogenase complex E2 (PDC-E2), branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2), and 2-oxo glutarate dehydrogenase complex E2 (OGDC-E2). However, there has been no information as to whether there is a difference in serological response between men and women. Using the serological hallmark of antimitochondrial antibodies (AMAs) and taking advantage of the availability of recombinant mitochondrial autoantigens, investigations were performed to determine if there were any serological differences between men and women with PBC. METHODS: Sera were collected from 88 patients with PBC, of whom 46 were men and 42 were women. Using a combination of immunoblotting and enzyme-linked immunoabsorbent assay (ELISA) against beef heart mitochondria (BHM), recombinant PDC-E2, BCOADC-E2, and OGDC-E2, we determined the relative autoantibody reactivities of our study population. RESULTS: Both men and women with PBC produced high titer antimitochondrial antibodies. The frequency of reactivity was similar in both groups and included, in descending order, PDC-E2, E3BP (Protein X), BCOADC-E2, and finally OGDC-E2. More importantly, antigenic specificity was nearly identical regardless of gender. CONCLUSIONS: AMAs are the serological hallmark of PBC in both men and women, and there is no significant difference in reactivity between the two groups of patients.

Adult↗
PubMed1999

Evidence for the role of environmental agents in the initiation or progression of autoimmune conditions.

The concordance of autoimmune disease among identical twins is virtually always less than 50% and often in the 25-40% range. This observation, as well as epidemic clustering of some autoimmune diseases following xenobiotic exposure, reinforces the thesis that autoimmune disease is secondary to both genetic and environmental factors. Because nonliving agents do not have genomes, disease characteristics involving nonliving xenobiotics are primarily secondary to host phenotype and function. In addition, because of individual genetic susceptibilities based not only on major histocompatibility complex differences but also on differences in toxin metabolism, lifestyles, and exposure rates, individuals will react differently to the same chemicals. With these comments in mind it is important to note that there have been associations of a number of xenobiotics with human autoimmune disease, including mercury, iodine, vinyl chloride, canavanine, organic solvents, silica, l-tryptophan, particulates, ultraviolet radiation, and ozone. In addition, there is discussion in the literature that raises the possibility that xenobiotics may also exacerbate an existing autoimmune disease. In this article we discuss these issues and, in particular, the evidence for the role of environmental agents in the initiation or progression of autoimmune conditions. With the worldwide deterioration of the environment, this is a particularly important subject for human health.

Anilides↗
PubMed1998

Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.

The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role of T cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC-E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 36-49 and OGDC-E2 peptide 100-113 thereby identifying a common T cell epitope "motif" ExETDK. The peptide 163-176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.

Adult↗
PubMed1998

Monoclonal antibodies to mitochondrial E2 components define autoepitopes in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of antimitochondrial Abs (AMA). The autoantigens recognized by AMA are the E2 components of the pyruvate dehydrogenase complex (PDC-E2), the branched chain 2-oxoacid dehydrogenase complex E (BCOADC-E2), and the 2-oxoglutarate dehydrogenase complex E (OGDC-E2). Previous studies using murine monoclonal and human combinatorial Abs to PDC-E2 have demonstrated an intense linear staining pattern in the apical region of biliary epithelial cells (BEC) in PBC but not control liver. We therefore examined whether mAbs to the other mitochondrial autoantigens BCOADC-E2 and OGDC-E2 demonstrated disease-specific patterns of reactivity. Using an expressed recombinant "trihybrid" protein containing the lipoyl domains of PDC-E2, OGDC-E2, and BCOADC-E2, we immunized BALB/c mice to produce 35 mAbs specific for one or more of the above mitochondrial autoantigens. Seven of these mAbs uniquely stained the apical region of BEC in PBC. Of these seven, one was reactive to PDC-E2, two recognized BCOADC-E2, three were reactive to OGDC-E2, and one recognized all three Ags. Our current data demonstrate that, similar to our previous studies regarding PDC-E2, mAbs to BCOADC-E2 and OGDC-E2, or a molecule that cross-reacts with the inner lipoyl domain of all three enzymes, also show a uniquely intense staining pattern in the apical region of BEC in patients with PBC when compared with diseased controls. The abundance of such disease-specific determinants in the target cells of PBC raises interesting possibilities regarding the role of these autoantigens in the pathogenesis of this disease.

Animals↗