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At least 19 recordsLinked to original sources

Non-organ specific & organ specific antibodies in rheumatoid arthritis.

Fifty patients of rheumatoid arthritis clinically diagnosed (by ARA criteria) were studied for both non-organ specific [rheumatoid factor (RF), anti-nuclear antibodies (ANA), extractable nuclear antibody (ENA), granulocyte specific anti-nuclear antibody (GS-ANA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA)] and organ specific, [anti-adrenal (AAA), anti-islet cell (ICA), antithyroid antibody (ATA) and anti-parietal cell (PCA)] auto antibodies. RF was positive in 80 per cent of patients. ANA was positive in 44 per cent of patients, ENA in 62 per cent, SMA in 20 per cent, AMA in 18 per cent and GS-ANA in 68 per cent. Of the organ specific antibodies, PCA was demonstrable in 28 per cent of the patients and none of the other antibodies were present. Circumstantial evidence indicates that ANA and GS-ANA are not synonymous but independent, cross-reacting entities and the presence of both increase the sensitivity (94%) of diagnosis of RA.

Adolescent↗

Non-organ specific & organ-specific auto-antibodies in hepatitis-B virus associated glomerulonephropathies.

Eighty eight patients of glomerulonephropathies (HBsAg positive 67; HBsAg negative 21) and 88 matched and healthy controls were screened for non-organ specific autoantibodies-ANA, AMA, ASMA and APCA by indirect immunofluorescent technique. The 2.3 per cent positivity in the test group and the 8 per cent positivity in the control group did not suggest the involvement of hepatitis-B virus (HBV), as an influencing or associated agent. When 48 patients with glomerulonephropathies and 23 controls were screened for liver cell membrane (LMA) and renal cell membrane antibodies (RMA) by indirect immunofluorescent technique using isolated rat hepatocytes and renal cells, 79.2 per cent LMA positivity was seen in the HBsAg positive group and 41.7 per cent in the negative group and RMA positivity was 58 per cent in the positive group and 25 per cent in the negative group. Simultaneous positivity for both LMA and RMA was recorded in 50 per cent of the HBsAg positive patients and 15.7 per cent of the negative ones. The results suggest the possibility of an organ specific autoimmune trigger more frequently in HBV associated glomerulonephropathy.

Antibody Specificity↗

[Detection of organ-specific and organ non-specific autoantibodies in the serum of sterile couples].

Sera from 150 infertile and 50 fertile couples were examined for organ-specific and non-organ-specific antibodies by indirect immunofluorescence tests on unfixed cryostat sections. Adrenocortical antibodies to zona fasciculata cells were found in 4 females and 2 males of infertile couples. Parietal cell antibodies were demonstrated in 4 females and 2 males of infertile couples. Parietal cell antibodies were demonstrated in 4 female and 3 male sera. Antibodies to mitochondria could be found in 14 fertile and 72 infertile couples. Antinuclear antibodies occurred in 2 fertile and infertile couples. Smooth muscle antibodies were found more often in infertile than fertile couples. Glomerular, skeletal muscle and reticulin antibodies were detected only in infertile couples. The detection of autoantibodies can help to elucidate immune reactions causing infertility.

Adrenal Cortex↗

Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians.

In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.

Adult↗

Organ specific metastasis with special reference to avian systems.

Many malignant tumors demonstrate a definite propensity for metastasis to specific organs despite the fact that tumor cells with the potential for metastasis may circulate randomly throughout the body. Current concepts of organ specific metastasis (OSM) center around the generation of tumor cell variants with enhanced capacity for metastasis to specific organs. At present three hypotheses, mechanical, seed and soil, and specific tumor cell adherence (STCA), stand out as possible explanations for OSM. These possible mechanisms of OSM are by no means mutually exclusive. Recent efforts to understand OSM have included the selection of organ-specific metastasizing variants from tumor cell lines and an examination of their surface and metastatic properties. OSM-selected cell lines from many different tumor systems have been used to examine the relative contributions of the three mechanisms. While examples of each mechanism have been reported, the relative contributions of each for different tumor systems may differ substantially. Therefore, generalizations about the behavior of tumors based on studies with just a few tumor lines and systems may not be valid. There is substantial evidence that cell surface molecules are important in the process of OSM and homing of lymphocytes to specific lymph nodes. Monoclonal antibodies have been produced against putative cell surface receptors and initial biochemical characterization has begun. There is much evidence that cell surface glycoconjugates can serve as specific recognition structures on normal cells and in addition, may play important roles in OSM. The role of these carbohydrates is discussed. The chick embryo as a model system is discussed as it offers several advantages for the study of metastasis in general and OSM in particular. A variety of human and murine tumors, including some freshly isolated, have been shown to grow and metastasize in these embryos. Furthermore, cell lines which have been selected for OSM in adults show similar patterns of metastasis in chick embryos indicating that this system may be an especially attractive one for the analysis of OSM.

Animals↗

Organ-specific and non-organ-specific lymphocyte receptors for vascular endothelium.

The recirculation of lymphocytes from blood to lymph and back to blood is necessary for the proper functioning of the immune system as it facilitates interactions between antigen-reactive clones of lymphocytes and antigen-presenting cells. The first step in the emigration of a blood-borne lymphocyte into either a secondary lymphoid organ or an inflammatory lesion is its adherence to vascular endothelial cells (EC) lining unique post-capillary venules known as high endothelial venules (HEV). Several groups have recently cloned and sequenced genes which may encode organ-specific lymphocyte receptors for the EC of such HEV. The extracellular portion of the putative murine lymphocyte homing receptor for peripheral lymph node HEV is composed of an N-terminal lectin-like domain, followed by an epidermal growth factor-like domain, and then two identical repeating domains which are homologous to a number of complement-binding proteins. A hydrophobic transmembrane domain and a cytoplasmic tail complete the structure. A very similar gene structure has been reported for a cytokine-inducible EC surface protein which is involved in neutrophil-EC adhesion in vitro. In marked contrast, the gene for a putative human lymphocyte homing receptor appears to belong to a gene family which encodes cell-surface molecules with receptor activity for extracellular matrix (ECM) proteins. Similarly, the cell-surface molecule which appears to be the murine lymphocyte receptor for Peyer's patch HEV is homologous, if not identical, to the human VLA-4 molecule, another receptor with binding activity for an ECM protein. It has also been demonstrated that lymphocyte function-associated antigen 1 (LFA-1) acts in a non-organ-specific manner to mediate lymphocyte-EC adhesion. Finally, other non-organ-specific lymphocyte adhesion molecules for EC may include CD4 and CD8 (which bind to class II and class I MHC antigens, respectively), and CD2 (which binds to LFA-3).

Animals↗

Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

OBJECTIVE: The aim of the study was to assess the complex of autoantibodies which can be detected in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a rare autosomal recessive disease in which the extent of autoimmunity is still unknown. DESIGN: Antibodies (A) to parathyroid glands, adrenal cortex (AC-A), ovary and testis (steroid cell antibodies, SC-A), pancreatic islet cells (IC-A), gastric parietal cells, and non-organ-specific antigens were investigated in 11 APECED patients living in the Salento region of southern Italy. Further measurements included antibodies to cytochrome P450 (CYP) enzymes: cholesterol side-chain cleavage enzyme (CYP11A), 21-hydroxylase (CYP21) and 17alpha-hydroxylase (CYP17); and to glutamic acid decarboxylase 65-kDa isoform (GAD65), tyrosine phosphatase-like protein IA2, thyroglobulin (TG), thyroperoxidase (TPO), thyrotropin receptor, liver CYP enzymes and intrinsic factor. METHODS: Antibodies to organs and subcellular fractions were detected by immunofluorescence. Radiobinding, immunoradiometric, and immunoblotting assays were used for the other measurements. RESULTS: AC-A and SC-A were positive in all sera; among antibodies to adrenal CYP enzymes, only CYP21-A were present in all the patients with Addison's disease of short-medium duration (<15 years). Of three patients with Addison's disease of long duration (>15 years), two tested positive for antibodies to all three CYP enzymes, and the other for only CYP11A-A. In all sera CYP11A-A and/or CYP17-A were found. Two patients tested positive for both IC-A and GAD65-A, one for both IC-A and IA2-A, and one for GAD65-A; the fasting C-peptide assay showed no statistical difference between these four subjects and the others. All four hypothyroid patients were positive for TPO-A, while two of them were positive and two were negative for TG-A; two euthyroid subjects had positivity for TG-A. Liver-kidney microsomal antibodies reacting against the CYP2A6 were detected in two patients with autoimmune hepatitis. All but one sera contained anti-nuclear antibodies at a titre ranging between 1:20 and 1:80; however, only two patients had a connective tissue disease (Sjögren's syndrome). CONCLUSIONS: Several autoantibodies may be detected in any APECED patient. Our data confirm that CYP21-A and TPO-A are major autoantibodies involved in APECED-associated Addison's disease and hypothyroidism respectively, while CYP11A-A and CYP17-A correlate with positivity for SC-A. Markers of islet cell autoimmunity are frequent, but prevalence and modalities of progression to overt beta-cell failure have to be clarified. Low-titre non-organ-specific autoantibodies are a feature of autoimmunity in APECED, but their role has yet to be fully explained.

Adolescent↗

[Detection of stage specific and organ specific human brain antigens during embryogenesis].

The rabbit antisera were obtained against the water soluble antigens of the brain of 8--10 weeks old human foetuses. Three groups of specific antigens were identified in the brain of human foetuses: 1) antigens common for the embryonic brain and other organs of the same age; 2) antigens common for the embryonic brain and some organs of the adult organism; 3) stage (phase)-specific brain antigens present only in the brain between the 8th and 10th weeks of pregnancy.

Animals↗

Organ-specific autoantibodies in non-organ-specific autoimmune diseases with special reference to rheumatoid arthritis.

Sera from 367 patients with rheumatoid arthritis (RA) and from 102 patients with other non-organ-specific (NOS) autoimmune diseases were examined for the presence of organ-specific (OS) autoantibodies. The incidence of these OS autoantibodies was not increased in patients with NOS autoimmune diseases with the exception of thyroglobulin antibodies, which were significantly more frequent in RA (P less than 0.001) and in Sjögren's syndrome (P less than 0.05) patients than in normal controls. Investigation of 169 patients with OS autoimmune diseases did not reveal an increased prevalence of NOS autoantibodies. In RA patients, OS autoantibodies correlated with NOS autoantibodies (P less than 0.04) and with HLA-DR3 antigen (P less than 0.01).

Adolescent↗

Detection of a cell-surface antigen correlated with organ-specific metastasis.

Despite the fact that tumour cells with the potential for metastasis may circulate randomly, many demonstrate a preference for specific organs. Recently, several investigators have selected variant tumour cell lines with enhanced capacity to metastasize to specific organs, mainly using the spontaneously originating B16 melanoma cell line of the mouse and tumour variants with enhanced capacity to metastasize to the lungs, brain and liver. We previously reported the derivation of a liver-specific metastatic variant of a Marek's disease (MD) virus-transformed, non-producer lymphoma cell line. MD is a naturally occurring, herpes virus-induced, T-cell lymphoma of chickens which bears pathological and aetiological similarities to Burkitt's lymphoma in man. This makes MD a useful model for study. One similarity is the pattern of metastasis in which both lymphomas induce a high incidence of ovarian and liver lesions. We now report the existence of a cell-surface antigen, detectable by a monoclonal antibody, correlated with organ-specific metastasis.

Animals↗

Specific organ metastases of human melanoma cells injected into the arterial circulation of nude mice.

The purpose of this study was to examine whether organ specific metastasis can be produced by different subpopulations of cells isolated from a single human melanoma. Three clones, SB1, SB2, SB3, and a variant line SB1 Asc (obtained from ascites fluid after i.v. inoculation of SB1 cells in a nude mouse) - all isolated from a primary human cutaneous melanoma - were inoculated into the left ventricle (i.c.) or intravenously (i.v.) into nude mice. Three to 16 weeks later, the animals were killed and autopsied. The clones produced different patterns of metastasis. Three to 4 weeks after i.c. inoculation of 2 x 10(6) cells, cells of clone SB1 produced numerous rapidly progressing metastases in the brain, whereas cells of SB1 Asc produced large metastases in the adrenals and sometimes in the ovaries. Cells of clones SB2 and SB3 produced a few small metastases without any characteristics pattern. The initial arrest of tumor cells in various organs did not predict the outcome of metastasis. This conclusion is based on studies of distribution and fate of tumor cells labeled with 111Indium Oxine. Therefore, organ specific metastasis produced by human melanoma cells inoculated i.c. into nude mice is likely to depend on the interaction of unique metastatic cells with organ environment.

Animals↗

Organ-specific metastases in melanoma: experimental animal models.

Metastases from certain primary tumors frequently exhibit specific organ preference. Animal models have been developed to induce in a reproducible fashion the formation of organ-specific metastases by malignant melanoma cells. Some of these models rely on the use of immunodeficient mice, which can support the growth of murine as well as human malignant melanomas. Moreover, immunodeficient mice, because of their diminished ability to mount an effective immune response, allow the expression of malignant properties (e.g., preferential colonization of certain organs), which are intrinsic to transplanted melanoma cells. This review discusses the relevant factors (and limitations) of some of the animal models used to study the in vivo properties of melanoma cells.

Animals↗

Particularities of the vasculature can promote the organ specificity of autoimmune attack.

How certain autoimmune diseases target specific organs remains obscure. In the 'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic antibodies caused macromolecular vasopermeability localized to sites destined to develop arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and FcgammaRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcRgamma-expressing cells in an organ distant from the joint were required. Histamine and serotonin were critical, and systemic administration of these vasoactive amines recapitulated the joint localization of immune complex-triggered vasopermeability. We propose that regionally distinct vascular properties 'interface' with immune effector pathways to foster organ-specific autoimmune damage, perhaps explaining why arthritis accompanies many human infectious and autoimmune disorders.

Animals↗

Gene expression profiling of tumor xenografts: In vivo analysis of organ-specific metastasis.

Mammary carcinoma frequently metastasizes to specific organs, including the regional lymph nodes, the lung and bone marrow. The mechanisms that guide organ-specific metastasis and the molecular players that are involved remain to be established. To gain insight into this problem, we used an orthotopic model of breast cancer in which the MDA-MB-435 cells are implanted into the mouse mammary fat pad. Sublines that preferentially metastasized to specific sites were isolated by excising metastatic tumors and growing explants of these tumors in culture. Cells lines that preferentially metastasize to the lymph node and thoracic cavity were obtained. The gene expression profiles of primary tumors from these sublines were then compared with cDNA arrays containing 5,800 known genes. In tumors that preferentially metastasize to the lymph node, several genes encoding adhesion and matrix proteins were upregulated. Genes encoding proteins involved in metabolism were downregulated. One of the upregulated genes in lymph-homing tumors was CD73. Immunohistochemistry showed that the CD73 protein is also upregulated in primary tumors of this cell line and that its expression is elevated in the lymph node metastases. CD73 is a transmembrane protein that has previously been implicated in the homing of normal lymphocytes to the nodes. This raises the hypothesis that tumors preferentially metastasize to lymph nodes by using CD73 to mimic part of the lymphocyte homing process.

5'-Nucleotidase↗

Organ-specific (localized) synthesis of Ig light chain amyloid.

Ig amyloidosis is usually a systemic disease with multisystem involvement. However, in a significant number of cases amyloid deposition is limited to one specific organ. It has not been determined if the Ig light chain (LC) amyloid precursor protein in localized amyloidosis is synthesized by circulating plasma cells with targeting of the amyloid fibril-forming process to one specific organ, or whether the synthesis of Ig LC and fibril formation occurs entirely as a localized process. In the present study local synthesis of an amyloid fibril precursor LC was investigated. Amyloid fibrils were isolated from a ureter that was obstructed by extensive infiltration of the wall with amyloid. Amino acid sequence analysis of the isolated fibril subunit protein proved it to be derived from a lambdaII Ig LC. Plasma cells within the lesion stained positively with labeled anti-lambda Ab and by in situ hybridization using an oligonucleotide probe specific for lambda-LC mRNA. RT-PCR of mRNA extracted from the tumor and direct DNA sequencing gave the nucleotide sequence coding specifically for the lambdaII amyloid subunit protein, thus confirming local synthesis of the LC protein.

Aged↗