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PubMed2004

Organ-specific antigens of Clonorchis sinensis.

This study was carried out to find out specific proteins from different organs of Clonorchis sinensis. Crude extract, organ-specific and excretory-secretory (ES) proteins were analyzed by immunoblot with infected human sera. The bands of 7- and 17-kDa were main component of intestinal fluid and ES protein and commonly found in all organspecific proteins. The 17-kDa protein was observed from ES antigen, intestinal fluid, eggs and sperms, 26- and 28-kDa proteins were from the uterus, vitellaria, and ovary, and 34-, 37-, 43- and 50-kDa proteins were mainly from the testis and sperms. Serum of mice immunized with sperms reacted to the 50-kDa protein by immunoblotting and immunohistochemical staining showed a positive reaction at the seminal receptacle and seminiferous tubule. The present results show that the 7-kDa protein is a common antigen of every part or organ of C. sinensis, but different organs express their specific antigenic protein bands.

Animals↗
PubMed1986

Fetal allograft survival in immunocompetent recipients is age dependent and organ specific.

This study explores whether fetal allograft survival is age dependent and organ specific. Fetal rat tissue (renal, gonadal, hepatic) from the third trimester of gestation (days 15-21) was transplanted into 306 outbred adult rats for 10-30 days. Grafts were studied by morphometric and histologic analysis. Ten days after implantation, renal tissue (N = 75) from late gestation (days 19-21) showed no increase in size. In contrast, 17-day fetal grafts (N = 20) grew 6.8 +/- 3.4 times,* while 15-day fetal grafts (N = 28) grew 17.5 +/- 6.1* times. (The symbol "*" indicates p less than 0.05, compared to original size). Twenty days after implantation, these 15-day fetal grafts (N = 20) grew 48.8 +/- 17.7* times. Ten days after grafting, the younger fetal tissue showed excellent maturation of renal elements and no sign of rejection; older fetal grafts had poor renal architecture and a dense lymphocytic infiltrate. The 15-day fetal gonadal tissue (N = 18) showed a moderate 10.6 +/- 3.2* increase in size while the 15-day hepatic grafts (N = 16) were regularly rejected within 10 days. Selected fetal allografts from early in the third trimester can not only survive but can grow and mature in an immunocompetent recipient. This fetal graft growth appears to be both age dependent and organ specific. The use of fetal organs may broaden the potential pool for transplantation. However, further studies are needed to define the ontogeny of graft acceptance.

Age Factors↗
PubMed1991

Generation of monoclonal antibodies directed against organ-specific endothelial cell surface determinants.

Organ-specific determinants expressed on the luminal surface of vascular endothelia are often unstable when cells are removed from their normal tissue environment and grown in culture. Unspecific endothelial cells of large vessel origin [e.g., bovine aorta (BAEC)] can be modulated to express and preserve such determinants when they are grown on the extracellular matrix of the desired organ. Lung matrix-modulated BAEC were used here to generate MAb against lung-specific vascular endothelia. Immunization was accomplished with outside-out membrane vesicles obtained by incubating BAEC monolayers grown on lung matrix with a low-strength paraformaldehyde solution. In four of the six fusions performed, this active immunization was preceded by passive immunization with mouse antiserum directed against membrane vesicles from BAEC grown on plastic. Among the growing hybrids, 7.6% secreted MAb that bound efficiently to both BAEC grown on lung-derived matrix and BAEC grown on plastic, while 3.5% (50) secreted MAb that bound primarily to BAEC grown on lung matrix. The fusion data show that only a passive/active immunization protocol yielded MAb directed against lung-specific endothelia. For example, MAb 6D3 and 5F5 selectively recognized endothelia from small- and medium-sized venules of bovine lungs, but failed to react with endothelial cells in other organs and tissues.

Animals↗
PubMed1993

[Medico-legal studies on detection of organ-specific antigens].

When the organs have been injured, specific antigens pertaining to the organs could be expected to be released into the circulation and/or adhere to the weapons which has inflicted the damage to the organs. We could thus be able to identify the injured organs, if we could detect the antigens specific to the organs in blood of the victim and/or in bloodstains left on the weapons. 1. Liver-specific antigen (LSA). The liver-specific antigen (LSA) was purified from the human liver and was showed to have a molecular mass of 52 kDa and pI of 5.8-5.9. Anti-human LSA antibody only reacted with the liver extract using immuno-dot-blotting technique, and depending on the immunohistochemistry, this antigen was located within the cytoplasm of hepatocytes. The human LSA was proved to be a novel protein, isolated from the human liver, by the NH2-terminal amino acid sequence analysis. Anti-human LSA Fab'-peroxidase conjugate was prepared and a highly sensitive and specific sandwich enzyme immunoassay for human LSA was developed. The detection limit of this assay was 0.52 pg/tube. The LSA levels in the serum and blood of cadavers with liver injuries were markedly increased. These findings suggest that the human LSA will become a useful marker for detecting liver injury. 2. Sucrase-Isomaltase (SI). A sandwich enzyme immunoassay for SI, a dimeric digestive enzyme, was developed using pig as a model animal. SDS-solubilized proteins from the small intestine contained at least 50-fold larger SI than those from the other organs. Significant amount of SI could be detected in small intestinal contents and in stains left on the knife which had been stabbed into the small intestine. These results suggested that SI was a possible forensic marker for small intestinal injuries, although human SI remained to be examined. 3. Cardiac Troponin I (cTnI). The purpose of our study is to identify injuries to the heart from a small amount of blood quickly and accurately by using a sensitive enzyme immunoassay for cardiac troponin I (cTnI), a heart specific protein. Accordingly we purified cTnI from bovine cardiac muscle and prepared the antibody against cTnI in order to develop this assay. We furthermore investigated the usefulness of this antibody by immuno-dot-blotting. As the result, it was confirmed that this antibody reacted against only heart. 4. Dystrophin. The purpose of this work is to develop a method to determine skeletal muscle injuries using muscle-specific substances. Dystrophin was purified from SDS-solubilized bovine skeletal muscle.

Animals↗
PubMed1983

Leukocyte alkaline phosphatase: another organ-specific alkaline phosphatase.

We have used enzyme specific inhibitors and heat inactivation to distinguish Leukocyte alkaline phosphate (LAP) from other organ-specific alkaline phosphatases as well as to compare LAP from normal granulocytes and leukemic cells with elevated LAP. The heat inactivation and inhibition curves of LAP are quite different from those of other organ-specific alkaline phosphatases. The inhibition curves and heat inactivation characteristics of LAP from normal granulocytes and that obtained from chronic granulocytic leukemia (CGL) blast phase cells with elevated LAP are identical. These data suggest that LAP is distinct from other organ-specific alkaline phosphatases, particularly placental alkaline phosphatase. We also conclude that the LAP present in cells with elevated levels is very similar or identical to that of normal granulocytes.

Alkaline Phosphatase↗
PubMed1996

The potential of organ specific toxicity for predicting rodent carcinogenicity.

Relationships between organ specific toxicity (specifications of the presence or absence of 43 morphological effects in 32 organs) observed from 13-week subchronic studies and rodent carcinogenicity were investigated by manually measuring the concordance of each feature and also automatically using the RL (Rule Learner) induction program. Of the 32 organs, the presence or absence of any effect in liver or kidney was found very relevant to rodent carcinogenicity. While the concordance of Salmonella genotoxicity with rodent carcinogenicity was only 60%, the battery of liver and kidney was 74% accurate with 75% sensitivity and 71% specificity. Further, using the RL program, rule sets based on organ specific toxicity together with the default predictions based on Salmonella mutagenicity were on average 80% accurate with 83% sensitivity and 82% specificity.

Animals↗
PubMed2006

Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice.

Factors that determine the spectrum of target organs involved in autoimmune destruction are poorly understood. Although loss of function of autoimmune regulator (AIRE) in thymic epithelial cells is responsible for autoimmunity, the pathogenic roles of AIRE in regulating target-organ specificity remain elusive. In order to gain insight into this issue, we have established NOD mice, an animal model of type 1 diabetes caused by autoimmune attack against beta cell islets, in which Aire has been abrogated. Remarkably, acinar cells rather than beta cell islets were the major targets of autoimmune destruction in Aire-deficient NOD mice, and this alteration of intra-pancreatic target-organ specificity was associated with production of autoantibody against pancreas-specific protein disulfide isomerase (PDIp), an antigen expressed predominantly by acinar cells. Consistent with this pathological change, the animals were resistant to the development of diabetes. The results suggest that Aire not only is critical for the control of self-tolerance but is also a strong modifier of target-organ specificity through regulation of T cell repertoire diversification. We also demonstrated that transcriptional expression of PDIp was retained in the Aire-deficient NOD thymus, further supporting the concept that Aire may regulate the survival of autoreactive T cells beyond transcriptional control of self-protein expression in the thymus.

Animals↗
PubMed1984

Total, and organ-specific, noradrenaline plasma kinetics in essential hypertension.

We have developed radiotracer techniques, based on measurement of the rate of spillover of noradrenaline to plasma, to simultaneously estimate total, and organ-specific, sympathetic nervous activity in humans. In 27 unmedicated subjects without renal or liver disease, or cardiac failure, regional noradrenaline spillover rates were as follows: lungs 33% of total noradrenaline release to plasma, kidneys 22%, skeletal muscle 20%, hepatomesenteric 9%, skin 5%, and heart 3%. These findings have relevance to numerous previous studies on the importance of the sympathetic nervous system in the pathogenesis of human essential hypertension. The indices of overall sympathetic nervous tone which have been used, such as measurements of plasma noradrenaline concentration or total NA release to plasma, are seen to be not sufficiently specific, since the organs and regions thought to be central to hypertension pathogenesis (kidney, heart, splanchnic circulation) are responsible for no more than 35% of all noradrenaline released to plasma. Organ-specific noradrenaline spillover measurements are better suited to the elucidation of any sympathetic nervous system pathophysiology in human hypertension. Early results point to an increase in renal sympathetic tone in young patients with essential hypertension.

Humans↗
PubMed2000

Thyroid autoimmunity and its association with non-organ-specific antibodies and subclinical alterations of thyroid function in women with a history of pregnancy loss or preeclampsia.

Following the observation that non-organ-specific antibodies are related with pregnancy loss and preeclampsia, the role of organ-specific antibodies is currently being extensively investigated. The aim of this study was on the one hand to evaluate the incidence of antithyroid antibodies in a study group of 69 women with a history of early pregnancy loss (subgroup 1), foetal death (subgroup 2) or preeclampsia (subgroup 3) and in a control group, on the other hand to assess the possible association of these autoantibodies with non-organ-specific antibodies and subclinical alterations of thyroid function in the study group. Antithyroid antibodies were present in 26/69 (37.7%) women of the study group (37.9% in subgroup 1; 40.9% in subgroup 2; 33.3% in subgroup 3) and in 10/69 (14.5%) of controls, the difference being statistically significant. A significant difference in the distribution of antibodies to thyroglobulin and thyroid peroxidase was found in subgroup 2. In the study group, the incidence of antiphospholipid antibodies was not significantly different in women positive (26.9%) and negative (34.9%) for antithyroid antibodies. Also, the overall incidence of subclinical alterations of thyroid function in the study group was significantly different in women positive (53.8%) and negative (16.2%) for thyroid autoimmunity (P<0.02). The results of this study seem to confirm the association between thyroid autoimmunity and obstetric complications and suggest the usefulness of undertaking prospective studies in order to evaluate the reproductive outcome of women with a history of recurrent abortion, foetal death or preeclampsia and positivity for antithyroid antibodies.

Abortion, Habitual↗
PubMed2003

Idiopathic chronic cough: association with organ specific autoimmune disease and bronchoalveolar lymphocytosis.

BACKGROUND: We have recently reported a strong association between organ specific autoimmune disease and idiopathic chronic cough and have suggested that cough may be caused by airway inflammation secondary to aberrant homing of activated lymphocytes to the lung. An immunopathological study was undertaken to test the hypothesis that idiopathic chronic cough is associated with lymphocytic airway inflammation. METHODS: Bronchoscopy, bronchial biopsies, bronchoalveolar lavage (BAL), and peripheral blood and BAL flow cytometry were performed in 19 patients with idiopathic chronic cough, 14 with explained chronic cough, and 11 normal subjects. RESULTS: Organ specific autoimmune disease or positive autoantibodies were present in eight of the 19 patients with idiopathic cough, in one of the 14 patients with explained cough, and in one of the 11 normal subjects. Median BAL fluid differential lymphyocyte counts were significantly higher in patients with idiopathic cough (10.0%) than in normal subjects (6.3%, 95% confidence interval of difference 1.5 to 11.9, p = 0.01) or patients with explained cough (5.2%, 95% CI of difference 2.0 to 10.4, p = 0.001). There were no differences in bronchial biopsy T lymphocyte counts between the groups. The mean (SE) proportion of CD3+ peripheral blood mononuclear cells expressing CD4 was significantly higher in normal subjects than in patients with idiopathic cough (69 (3)% v 58 (3)%, mean difference 11%, 95% CI of difference 2 to 20, p<0.02) but not than those with explained chronic cough (63 (2)%). There were no differences in BAL T lymphocyte phenotype between groups. CONCLUSION: BAL fluid lymphocytosis occurs in some patients with idiopathic chronic cough. The association of idiopathic chronic cough with organ specific autoimmune disease raises the possibility that this might be caused by lymphocyte homing from the primary site of autoimmune inflammation or the result of an autoimmune process in the lung.

Autoantibodies↗
PubMed2004

Idiopathic chronic cough and organ-specific autoimmune diseases: a case-control study.

The marked female predominance in cases of idiopathic chronic cough and its association with mild chronic lymphocytic airway inflammation suggests an underlying autoimmune process. We set out to test the hypothesis that idiopathic chronic cough is associated with other organ-specific autoimmune diseases in a case control study. Twenty-two patients with idiopathic chronic cough and 65 community-matched controls for age and sex who responded to a self-administered questionnaire were asked about the presence of autoimmune disease, other medical problems and drug history. All subjects were invited to have a blood test for an autoimmune screen. Thirteen out of 22 (59%) patients with idiopathic chronic cough and eight out of 65 (12%) age- and sex-matched controls reported organ-specific autoimmune disease (odds ratio 8.8; 95% confidence interval 2.4-31.8, P<0.001). Organ-specific autoantibodies were present in a significantly higher proportion of cases than controls (40% vs. 13%; P = 0.047). These findings suggest a relationship between idiopathic chronic cough and organ-specific autoimmunity.

Adult↗
PubMed2002

Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease.

Thymectomy on day 3 after birth (d3tx) depletes CD4+CD25+ regulatory T cells leading to multiple independent organ-specific autoimmune diseases. However, systemic autoimmune disease such as systemic lupus erythematosus has not been reported in d3tx mice. Herein, we investigate the effect of d3tx on spontaneous autoantibody response and immune complex glomerulonephritis (GN) in the lupus-prone (SWR x NZB)F1 (SNF1) mice. The d3tx SNF1 mice developed accelerated antibody responses to double-stranded DNA and DNA-histone complexes, and an increased frequency of activated CD4+ T cells. Unexpectedly, the renal histopathology and mortality from GN were significantly ameliorated in d3tx SNF1 mice, which concomitantly exhibited a Th2-biased antibody response. By 16 weeks, the d3tx mice had higher levels of total and autoantigen-specific IgG1, and at 12 months, the autoantigen-specific IgG2a was significantly below that of the sham thymectomized mice. These differences corresponded with reduction in total and autoantigen-specific IgG2a in the renal eluates of the d3tx mice. In addition, while all the mice had immune complex deposition in the mesangium and peripheral capillary loops of the glomeruli, IgG2a and C3 deposits restricted to the mesangial regions alone were more frequent in d3tx mice. D3tx SNF1 mice, protected from lupus-like GN, developed organ-specific autoimmune responses and diseases including prostatitis, orchitis and oophoritis, and antibodies to prostate, cardiac and skeletal muscle antigens. Therefore, d3tx paradoxically protects SNF1 mice from genetically prone lupus-like GN, yet promotes de novo organ-specific autoimmunity.

Animals↗
PubMed1985

Metastatic potential of B16 melanoma cells after in vitro selection for organ-specific adherence.

Heterogeneous primary tumors contain subpopulations of cells that differ in ability to metastasize to specific host organs. We have used cryostat sections of host organs to select for metastatic variants of B16 melanoma cells with increased adhesion to specific syngeneic tissues. By repeating the selection procedure with lung tissue, a subpopulation of cells was isolated that demonstrated a specific increase in binding to cryostat sections of mouse lung. This altered binding was reflected by a sixfold increase in the frequency of lung metastasis 21 d after tail vein injection of the tumor cells. In contrast, B16 melanoma cells selected on cryostat sections of mouse brain showed no increase in adhesion to brain or lung tissue and the metastatic pattern in vivo was not significantly different compared with the parent cell line. When cells selected for increased adhesion to cryostat sections of lung were further examined in vitro, they showed altered morphology and increased motility but no change in growth rate. These results demonstrate that alterations in the adhesive interactions between metastatic tumor cells and a specific host tissue can directly affect the frequency of metastasis to that tissue in vivo.

Animals↗
PubMed1992

The TATA box promoter region of maize Adh1 affects its organ-specific expression.

We have isolated two lineage-related Mutator (Mu3) transposon-induced Adh1 promoter mutants in maize: Adh1-3F1124 carries a duplicated TATA box and its revertant, Adh1-3F1124r17, bears a deleted TATA box. Both alterations lead to unique patterns of organ-specific ADH1 enzyme expression. Enzyme activity in Adh1-3F1124 sporophytic organs (scutellum and roots) is greatly reduced, while activity levels remain normal in the male gametophyte (pollen). Conversely, enzyme activity in Adh1-3F1124r17 roots and scutellum is partially restored, but is concomitantly reduced in pollen. Transcript analysis suggests (i) that the TATA box region of the Adh1 gene influences post-transcriptional processes in the male gametophyte but not in roots and (ii) that organ-specific transcription signals in the promoter are distinct from the previously identified anaerobic environment-specific cis-acting transcription signals. Different organs appear to provide surrogate TATA function in different ways, leading to organ-specific differences in the length of the Adh1 message 5' leader.

Alcohol Dehydrogenase↗
PubMed2006

Molecular analysis of early rice stamen development using organ-specific gene expression profiling.

Elucidating the regulatory mechanisms of plant organ formation is an important component of plant developmental biology and will be useful for crop improvement applications. Plant organ formation, or organogenesis, occurs when a group of primordial cells differentiates into an organ, through a well-orchestrated series of events, with a given shape, structure and function. Research over the past two decades has elucidated the molecular mechanisms of organ identity and dorsalventral axis determinations. However, little is known about the molecular mechanisms underlying the successive processes. To develop an effective approach for studying organ formation at the molecular level, we generated organ-specific gene expression profiles (GEPs) reflecting early development in rice stamen. In this study, we demonstrated that the GEPs are highly correlated with early stamen development, suggesting that this analysis is useful for dissecting stamen development regulation. Based on the molecular and morphological correlation, we found that over 26 genes, that were preferentially up-regulated during early stamen development, may participate in stamen development regulation. In addition, we found that differentially expressed genes during early stamen development are clustered into two clades, suggesting that stamen development may comprise of two distinct phases of pattern formation and cellular differentiation. Moreover, the organ-specific quantitative changes in gene expression levels may play a critical role for regulating plant organ formation.

Cluster Analysis↗
PubMed1986

Non-organ specific thermostable tissue antigens.

Thermostable ethanol insoluble antigens (BE antigens) were identified that occur in all human tissues and human dispersed cells, but which are absent from normal human serum. In contradistinction to previously described organ-specific BE antigens, these antigens were referred to as non-organ-specific tissue antigens (NOST). Antisera obtained by immunization of rabbits with BE preparations of human organs had been selected for being devoid of any organ specificity and had been absorbed by BE preparations of pooled human serum. Such antisera could be used as reagents for detection of NOST BE antigens in pathological human sera. Inhibition of enzyme immunoassay proved to be a convenient procedure for these studies. Inhibition of 35% or more was only exceptionally noted in studying sera of normal subjects 20-40 years old, but inhibition exceeding 35% (positive results) was noted in 48% of sera from subjects at the age of 70 years or more. A high incidence of positive results was also encountered in sera of patients with end-stage renal disease (30%), renal graft recipients (18%), and in patients with lymphoma or leukemia (44%), but interestingly enough, no positive tests were noted in patients with lepromatous leprosy.

Adult↗
PubMed1989

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese HLA antigens and organ-specific autoantibodies.

HLA phenotypes and haplotypes in relation to organ-specific autoantibody responses were studied in 82 Japanese patients with Type 1 (insulin-dependent) diabetes. HLA-DRw9 antigen and HLA phenotype of DRw9/X (X:not DR4) were increased in patients with organ-specific autoantibodies other than islet cell antibody (CP less than 0.02, RR = 4.02 and p less than 0.05 RR = 2.30, respectively); whereas HLA-DR4 antigen and HLA phenotype of DR4/X (X: not DRw9) were increased in those without the autoantibodies (CP less than 0.001, RR = 3.95 and p less than 0.01, RR = 2.46, respectively). HLA haplotype of Bw61-DRw9 was increased in patients with the autoantibodies (p less than 0.005, RR = 4.94), and HLA haplotype of Bw54-DR4 was increased in those without the autoantibodies (p less than 0.001, RR = 5.52). The relative risk of HLA-DR4/DRw9 was the highest among all HLA-DR phenotypes or genotypes in patients either with or without the autoantibodies. No association was, however, found between the incidence of islet cell antibody and HLA-DR phenotypes. These findings suggest that Type 1 diabetes among Japanese is immunogenetically heterogeneous as is Type 1 diabetes among Caucasians; and the differences in HLA-association of Type 1 diabetes among ethnic groups might give a clue to understanding of a role of HLA-antigens in the development of Type 1 diabetes.

Autoantibodies↗
PubMed1981

Goblet cell glycoprotein: an organ-specific antigen for gut. Isolation, tissue localization and immune response.

We report, for the first time, immune responses within two lines of inbred rats to a purified Lewis rat glycoprotein antigen which is organ-specific for intestine. The antigen was prepared by solubilization of gut epithelial cell-associated macromolecules, fractionation in ethanol, and molecular sieve chromatography over Sepharose 2B. Homogeneity of the end product (RGCG-PK1) was supported by results of both double diffusion in agar and SDS polyacrylamide gel electrophoresis. Amino acid analysis and specific sugar determination proved that RGCG-PK1 was not a classical mucin because of its comparatively high tyrosine and low galactosamine + glucosamine content, and the absence of glycosidic linkages to serine and threonine. Organ-specificity was shown by the ability of RGCG (but not liver homogenate) to inhibit precipitation and haemagglutination by heterologous specific sera. Organ-specificity was confirmed by the demonstration of RGCG-PK1-specific immunofluorescence staining of rat small and large intestine, but not esophagus, stomach or liver. RGCG-PK1 determinants within rat and human small bowel were found to be confined to goblet cells and intestinal glycocalyx. Anti-RCGC-PK1 serum showed no reactivity with highly purified xenogeneic mucins nor with syngeneic small bowel mucin. Specific antibody (as well as antibody-dependent cellular cytotoxicity) to RGCG was elicited and detected for up to 10 days in two lines of inbred rats, including the one (Lewis) from which the antigen was isolated. The duration and peak of the humoral immune response were abbreviated compared with that of a xenogeneic control glycoprotein studied in parallel, probably due to immunoregulatory mechanisms operative for self antigens.

Amino Acids↗