PubMed Health⌕ Search

Biomedical subjects

J Van De Water

Publications and source records attributed to J Van De Water.

14 recordsLinked to original sources
PubMed2003

Cocoa flavonols and procyanidins promote transforming growth factor-beta1 homeostasis in peripheral blood mononuclear cells.

Evidence suggests that certain flavan-3-ols and procyanidins (FP) can have a positive influence on cardiovascular health. It has been previously reported that FP isolated from cocoa can potentially modulate the level and production of several signaling molecules associated with immune function and inflammation, including several cytokines and eicosanoids. In the present study, we examined whether FP fractions monomers through decamers modulate secretion of the cytokine transforming growth factor (TGF)-beta(1) from resting human peripheral blood mononuclear cells (PBMC). A total of 13 healthy subjects were studied and grouped according to their baseline production of TGF-beta(1). When cells from individuals with low baseline levels of TGF-beta(1) (n = 7) were stimulated by individual FP fractions (25 microg/ml), TGF-beta(1) release was enhanced in the range of 15%-66% over baseline (P < 0.05; monomer, dimer, and tetramer). The low-molecular-weight FP fractions ( or=hexamer), with the monomer and dimer inducing the greatest increases (66% and 68%, respectively). In contrast to the above, TGF-beta(1) secretion from high TGF-beta(1) baseline subjects (n = 6) was inhibited by individual FP fractions (P < 0.05; trimer through decamer). The inhibition was most pronounced with trimeric through decameric fractions (28%-42%), and monomers and dimers moderately inhibited TGF-beta(1) release (17% and 23%, respectively). Given the vascular actions associated with TGF-beta(1), we suggest that in healthy individuals, homeostatic modulation of its production by FP offers an additional mechanism by which FP-rich foods can potentially benefit cardiovascular health.

Biflavonoids↗
PubMed2001

The lymphoid liver: considerations on pathways to autoimmune injury.

Immunologic injury in the liver involves immigrant T and B lymphocytes and a resident lymphoid population that comprises distinct lymphocytic cells and accessory cells. The forerunner to autoimmunity is breaching of natural self-tolerance and hence the disruption of a fundamental property of the immune system. Such breaching occurs by processes that include inflammatory activation of immunocytes and macrophages, spillage of intracellular constituents, and epitope mimicry by constituents of microorganisms, with these acting on a genetically conditional phenotype; compounding factors include aberrations of apoptosis, whether insufficient or excess. The downstream end requires specifically directed inflammatory leukocyte traffic as an essential component of autoimmune expressions in the liver. The culmination is an orchestrated attack on hepatocytes or biliary epithelial cells by multiple effector pathways. Progress in type 1 autoimmune hepatitis still requires knowledge of a disease-specific autoantigen(s) involved in T-cell reactivity, although such knowledge in type 2 autoimmune hepatitis, in which the known autoantigen is cytochrome P4502D6, has not yet been integrated into a clearly defined scheme of pathogenesis. For PBC there has been a very promising amalgamation of molecular knowledge of the mitochondrial autoantigens. Future insights require deeper analysis of molecular, genetic, macroenvironmental, and microenvironmental elements in predisposition.

Animals↗
PubMed2001

Immunoglobulin gene usage and immunohistochemical characteristics of human monoclonal antibodies to the mitochondrial autoantigens of primary biliary cirrhosis induced in the XenoMouse.

The immunodominant antimitochondrial antibody (AMA) response in primary biliary cirrhosis (PBC) is directed against the E2 component of pyruvate dehydrogenase (PDC-E2). The nature of the clonal selection process is unclear, and to address this issue, we took advantage of a transgenic technology, XenoMouse, that contains 80% of the human immunoglobulin (Ig) variable gene repertoire and can produce high-affinity human antibodies to virtually any immunogen without evidence of clonal bias. We immunized mice with PDC-E2 to obtain 13 HmAbs, including 4 IgG(2) and 9 IgM isotypes. Immunoglobulin gene analysis was unique and demonstrated a clonal bias; the immunoglobulin gene usage was considerably different from other antibody responses analyzed in XenoMouse systems. Four of the 13 mAbs recognized the inner lipoyl domain of PDC-E2, 2 of 13 recognized the entire PDC-E2 molecule, 4 of 13 recognized PDC-E2 and OGDC-E2, 1 of 13 recognized OGDC only, 1 recognized BCOADC-E2 only, and 1 recognized an unidentified 100-kd mitochondrial protein. Immunohistochemical staining using these HmAbs produced mitochondrial staining of septal bile ducts in both PBC and control livers. Ig gene analysis showed that 7 of 13 HmAbs used the V(H)3 and 4 of 13 used VH4 gene repertoire, respectively. Three of 7 V(H)3 antibodies used the same Ig VH3-21 gene family found in human AMA from patients with PBC. The CDRs of these autoantibodies were slightly mutated when compared with the sequences present within the Ig germline genes. In conclusion, the XenoMouse not only recapitulates the unique specificity and restriction of PBC patients, but indicates that the autoantibodies are derived from a restricted clonal selection process. Such data suggest that the original immunogen leads to somatic mutation without subsequent development of determinant spreading.

Amino Acid Sequence↗
PubMed2000

Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is often considered to be a dry gland disease caused by frequent involvement of salivary and lacrimal glands. Although high titers of antimitochondrial autoantibodies (AMA) have long been recognized in PBC, little is known about the presence of mitochondrial autoantigens in mucosal compartments such as saliva. We investigated saliva and sera in PBC patients and controls for the presence of AMA and mitochondrial antigens. In PBC saliva, AMA were detected in 45 of 49 (92%), with specificity directed against pyruvate dehydrogenase complex (PDC-E2) alone in 22 of 49 (45%), against PDC-E2 and branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 4 of 49 (8%), to PDC-E2 and 2-oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 9 of 49 (18%), and to the 3 antigens together in 10 of 49 (20%). Isotyping of the saliva AMA showed that 80% of the patients had immunoglobulin A (IgA) against PDC-E2, 18% had IgM-specific PDC-E2, and 35% had IgG specific PDC-E2. Similar to serum and bile anti-PDC-E2 IgA antibodies, the saliva autoantibodies localized their reactivity to the inner lipoyl domain of PDC-E2. Furthermore, saliva from patients with PBC but not controls inhibited pyruvate dehydrogenase enzyme activity in vitro. In addition, and of particular interest, we detected a molecule with a molecular weight corresponding to PDC-E2 (74 kd) in PBC but not control saliva. These findings make several important points: first, there appears to be localized mucosal immunity in the secretory system of PBC; second, AMA are readily detected in PBC saliva; and third, PDC-E2 may be present in the saliva of PBC.

Antibody Specificity↗
PubMed2000

Cocoa procyanidins and human cytokine transcription and secretion.

We examined whether cocoa, in its isolated procyanidin fractions (monomer through decamer), would modulate cytokine production at the levels of transcription and protein secretion in both resting and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC). In resting cells, interleukin (IL)-1beta and IL-4 gene expression from cocoa-treated cells varied markedly among the subjects tested. However, at the protein level, the larger fractions (pentamer through decamer) stimulated a dramatic increase in IL-1beta concentration (up to ninefold) with increasing degree of polymerization. Similarly, these larger fractions augmented IL-4 concentration by as much as 2 pg/ml, whereas the control displayed levels nearly undetectable. In the presence of PHA, gene expression also seemed to be most affected by the larger procyanidin fractions. The pentameric through decameric fractions increased IL-1 beta expression by 7-19% compared with PHA control, whereas the hexameric through decameric fractions significantly inhibited PHA-induced IL-4 transcription in the range of 71-86%. This observation at the transcription level for IL-1 beta was reflected at the protein level in PHA-stimulated PBMC. Significant reductions in mitogen-induced IL-4 production were also seen at the protein level with the hexamer, heptamer and octamer. Individual oligomeric cocoa fractions were unstimulatory for IL-2 in resting PBMC. However, when induced with PHA, the pentamer, hexamer and heptamer fractions caused a 61-73% inhibition in IL-2 gene expression. 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.

Biflavonoids↗
PubMed1999

Familial primary biliary cirrhosis in Hiroshima.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by the presence of anti-mitochondrial antibodies and chronic inflammatory destruction of septal and intrahepatic bile ducts. Although there are no obvious associations of PBC with MHC class I or class II genes, there appears to be a significant increased risk of developing disease within families. Clearly, a combination of genetic and environmental factors play a role in disease pathogenesis, although the relative contributions of each are unclear. In this study, we have taken advantage of the well-defined health-care system in Hiroshima prefecture, where PBC is a reportable disease. In the period 1988-1997, 156 new patients with PBC in a total population of 2,873,000 were diagnosed. These patients included 18 subjects that were derived from eight different families in which more than one family member had a history of PBC; this reflects a frequency of 5.1% and further shows that the prevalence of PBC is greatly increased in family members. Of interest, the median age of onset of PBC in second generation patients was much younger (33.4+/-10.8 years) compared to median disease onset in general patients with PBC in Hiroshima (55.6+/-12 years). In fact, it was striking that the onset of disease in family members often occurred within a few years of each other. We also noted that sera of affected members had similar AMA reactive profiles against recombinant PDC-E2, BCKD-E2 and OGDC-E2; the major autoantigens of PBC. Similar HLA types were found within affected members of a pedigree but the data is limited because of absence of similar typing of unaffected members. The increased family history of PBC, and the earlier onset of disease in second generation members, suggests that environmental agents are an important risk factor for the development of disease. We suggest that genomic analysis in familial PBC will be important to identify the mechanisms of genetic susceptibility.

Adult↗
PubMed1997

Primary biliary cirrhosis an epithelitis: evidence of abnormal salivary gland immunohistochemistry.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease of unknown etiology. Nearly 93% of patients with PBC exhibit evidence of focal sialoadenitis. In an earlier study, we reported evidence of aberrant expression of PDC-E2, or a mimeotope, in the salivary glands of patients with PBC that had Sjogren's syndrome. At the time of the previous study, data was not yet available regarding patients with PBC without sicca complaints. Therefore, to investigate the extent of salivary gland involvement in PBC, we collected lip biopsy sections from 9 PBC patients diagnosed as PBC by liver biopsy, without clinical or histologic features of Sjogren's syndrome and 9 PBC patients with established Sjogren's syndrome. Using immunohistochemical staining with both a murine monoclonal antibody. C355.1, and a human combinatorial antibody, SP4, we examined the ducts of these salivary glands for the presence of the characteristic aberrant staining pattern found in patients with PBC. We report that 6/9 PBC patients fulfilling established Sjogren's syndrome criteria and 6/9 PBC patients lacking features of Sjogren's syndrome showed intense staining of the ductal epithelial cells of the salivary gland. These data suggest that the PBC-specific antigen recognized by C355.1 and SP4 in bile duct epithelial cells is expressed aberrantly in the salivary gland in 66% of patients with PBC, independent of Sjogren's syndrome. This finding suggests a common disease process in these two tissues. Further, expression of this molecule may be an early marker of salivary gland involvement in patients with PBC.

Animals↗
PubMed1995

Abnormal expression of PDC-E2 on the apical surface of biliary epithelial cells in patients with antimitochondrial antibody-negative primary biliary cirrhosis.

The presence of antimitochondrial antibodies (AMA) is a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, the study of these autoantibodies has enabled much information to be accumulated about the specificity of this response. The autoantigens have been identified as components of a functionally related enzyme family, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E2 subunit (PDC-E2) has been determined to be the immunodominant autoantigen. Using a panel of mouse monoclonal antibodies and human combinatorial autoantibodies, it has been demonstrated that patients with PBC, but not controls, have an abnormal expression of either PDC-E2 or a cross-reacting molecule in the apical region of biliary epithelium. Others have shown a similar reaction using rabbit sera directed to PDC-E2. Our previous studies have concentrated on AMA-positive patients. In this study, the presence of PDC-E2, class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells of AMA-positive as well as AMA-negative patients is addressed. Most patients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region of the bile duct epithelial cells of "PDC-E2," increased IgA expression, and little major histocompatibility complex (MHC) class II staining in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E2 on the apical side of their biliary epithelium had anticentromere antibodies and Sjögren's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype.

University of California, Davis, line 200 and 206 chickens spontaneously develop an autoimmune syndrome that has many features analogous to human scleroderma, including dermal fibrosis, antinuclear antibodies and antibodies to type II collagen. These birds also have thymic subcapsular epithelial defects and an abnormality in T cell calcium influx and proliferation in response to both T cell receptor-dependent and -independent activators. To determine whether fibroblast activation is a contributing factor to development of skin fibrosis in line 200/206 chickens, as it is in human scleroderma, we studied the collagen, non-collagenous protein and glycosaminoglycan (GAG) production of 34 separate fibroblast lines derived from the normal and fibrotic skin of line 200 and 206 chickens and from the skin of control chicken lines 058 and 254. The mean +/- SEM 24-h incorporation of 3H-proline or 3H-glucosamine into extracellular collagen, non-collagenous protein or GAG by first passage fibroblast lines derived from the fibrotic skin of diseased birds was 1,526 +/- 136, 859 +/- 82 and 25.7 +/- 1.3 dpm/10(3) cells, respectively, while fibroblast lines derived from the skin of control birds produced only 341 +/- 36, 343 +/- 42 and 15.2 +/- 1.4 dpm/10(3) cells. Similar differences in results were recorded for cell-associated production, and when collagen and non-collagenous protein production were assessed using non-radioactive electrophoretic methods. The activated phenotype of the fibroblast lines derived from the fibrotic skin of diseased birds persisted through 10 cell doublings in tissue culture. However, the ratio of type I:III collagen and the profile of GAG types produced were similar in all fibroblast lines studied. These results suggest that fibroblast activation is responsible for the skin fibrosis observed in this avian model of scleroderma.

Animals↗
PubMed1992

Cardiovascular changes during laparoscopic cholecystectomy.

Although the technique of laparoscopic cholecystectomy has increasing appeal, physiologic data to support the safety of this procedure are lacking. We studied the cardiovascular changes in 16 patients undergoing laparoscopic cholecystectomy, using impedance cardiography as a noninvasive means of continuous monitoring of cardiac output. Serial measurements of mean arterial pressure (MAP), heart rate (HR), intraperitoneal pressure and expired carbon dioxide tension (PECO2) were also recorded. Results revealed a decrease of 30 percent (p < 0.001) in cardiac index and 5 percent (p = 0.089) in HR, along with increases of 15 percent (p < 0.001) in MAP and of 79 percent (p < 0.001) in the calculated total peripheral resistance index. This elevation in afterload could lead to both an increase in myocardial oxygen consumption and to the potential risk of myocardial ischemia and possibly infarction or congestive heart failure, or both, in patients who are susceptible. The data suggest that patients with a history of cardiac disease should have preoperative cardiac evaluation and be closely monitored during laparoscopic cholecystectomy, as in any other extensive operation.

Adult↗
PubMed1991

Selective abnormalities in the thymic microenvironment associated with avian scleroderma, an inherited fibrotic disease of L200 chickens.

As a prelude to deciphering the mechanisms of intrathymic T-cell maturation we produced a panel of 18 monoclonal antibodies (mAbs) against chicken thymic stromal elements. Eleven of these detected epithelial cells. They were: pan-epithelial; subcapsule and peri-vascular (pan type 1 epithelium); subcapsular, perivascular and medulla; medulla; or cortex. Of particular interest were the sub-specificities within these regions, especially the subcapsular region. Four mAbs stained both epithelial and non-epithelial cells in discrete regions. In addition, three mAbs recognized only non-epithelial cells. One identified macrophages scattered throughout the thymus, another the connective tissue and another the medullary vascular endothelium. These reagents have provided an extensive profile of the thymic stromal architecture and revealed that these cells are equally as complex as the T cells whose differentiation they induce and regulate. While the mAbs provide a valuable means for studying the mechanisms of normal thymopoiesis, their clinical significance is unknown. UCD line 200 chickens develop an autoimmune disease manifest by dermal and internal organ fibrosis, T cell infiltrates of skin and other affected organs and production of multiple autoantibodies. We have used our panel of mAbs to evaluate the thymic microenvironment in these autoimmunity-prone chickens. A comparative analysis with control chickens revealed striking deficiencies in the L200 subcapsular regions coupled with excessive expression of MHC class II antigens, particularly in the cortex. We hypothesize that these abnormalities induce altered T-cell differentiation, thereby predisposing the L200 chickens to autoimmune disease.

Animals↗
PubMed1978

Screening for lower extremity deep venous thrombosis. An improved plethysmographic and Doppler approach.

Noninvasive screening of the lower extremities for deep vein thrombosis was performed bilaterally on 1,118 patients. Impedance plethysmography alone was used in 868. Venography in 135 revealed an accuracy of 88%, with a false-negative rate of 5.3% and a false-positive rate of 18.6%. A combined ultrasonic Doppler and modified impedance technic was used in 250 patients. Venography in forty revealed an accuracy of 95%, with a false-positive rate of 10% and no undetected thrombi. The combined technic, emphasizing the more accurate modality in three anatomic areas, has proven sensitive, specific, and reliable as a screening test for deep venous thrombosis.

Doppler Effect↗