Spontaneous echocardiographic contrast (a swirling, smokelike haze that appears in blood during imaging) indicates a predisposition to thromboembolism, particularly in patients with atrial fibrillation and elevation of hematocrit, ESR, and serum fibrinogen.

Echocardiography, Transesophageal↗

PubMed1997

In situ nucleic acid hybridization of cytokines in primary biliary cirrhosis: predominance of the Th1 subset.

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of the intrahepatic bile ducts. It is generally believed that cellular immune mechanisms, particularly involving T cells, result in this bile duct damage. The relative strength of Th1 and Th2 responses has recently been proposed to be an important factor in the pathophysiology of various autoimmune diseases. In this study, we have attempted to identify the Th subset balance in PBC, by detection of cytokines specific to the two T-cell subsets, i.e., interferon gamma (IFN-gamma) for Th1 cells and interleukin-4 (IL-4) for Th2 cells. We analyzed IFN-gamma and IL-4 messenger RNA (mRNA) positive cells in liver sections from 18 patients with PBC and 35 disease controls including chronic active hepatitis C, extrahepatic biliary obstruction (EBO), and normal liver, using nonisotopic in situ hybridization and immunohistochemistry. Mononuclear cells expressing IFN-gamma and IL-4 mRNA were aggregated in inflamed portal tracts in PBC livers, but were rarely present in extrahepatic biliary obstruction, alcoholic fibrosis, or normal liver sections. The IFN-gamma and IL-4 mRNA positive cells in PBC livers were detected in significantly higher numbers than in control livers (P < .01). Moreover, IFN-gamma mRNA expression was more commonly detected than IL-4 expression in PBC livers, and the levels of IFN-gamma mRNA expression were highly correlated with the degree of portal inflammatory activity. IFN-gamma mRNA-positive cells were detected primarily around damaged bile ducts that were surrounded by lymphoid aggregates. The data indicate that Th1 cells are the more prominent T-cell subset in the lymphoid infiltrates in PBC.

Actins↗

PubMed1997

Persistence of autoantibodies against recombinant mitochondrial and nuclear pore proteins after orthotopic liver transplantation for primary biliary cirrhosis.

Primary biliary cirrhosis is an autoimmune disease characterized by high titer autoantibodies predominantly against mitochondrial antigens PDC-E2, BCOADC-E2 and OGDC-E2. Currently orthotopic liver transplant (OLT) is the major form of treatment for end-stage primary biliary cirrhosis (PBC), but it is still unclear whether the autoimmune response continues post-transplantation. In this study we took advantage of a well-defined collection of sera collected serially before and after liver transplantation. We assayed these sera for quantitative and isotype-specific titers of antibodies against a set of recombinant mitochondrial autoantigens. We also studied reactivity to gp210. Serum samples were taken before transplantation and at intervals of 6 months, 1, 2, and 3 years after OLT. Before OLT 24/35 patients were AMA-positive, including seven out of the 35 to PDC-E2 alone, eight to both PDC-E2 and OGDC-E2, six to both PDC-E2 and BCOADC-E2, two to BCOADC-E2 alone and one to OGDC-E2. Following OLT, the frequency of sera that responded to PDC-E2 alone increased from seven to 12/35. Similarly, reactivity to BCOADC-E2 slightly increased from two to four out of 35. However, there was an overall decrease in sera that responded to more than one antigen. Neither Ig isotype nor subclass of the autoimmune response changed following OLT. Findings with gp210 were similar, in that reactivity to gp210 was found in nine out of 35 patients pre-OLT; following OLT the frequency decreased to seven out of 35 patients. Overall, the titers of AMAs decline slightly during the first year post-OLT, but are equivalent to pre-OLT values by 6 months. Moreover, the antibody subclass/ isotype remained unchanged. These data suggest that the removal of a diseased PBC liver has little, if any, impact on the serological characteristics of PBC. Moreover, it provides information regarding the natural history of PBC, particularly on the long latency time for disease development.

Antibodies, Monoclonal↗

PubMed1997

Antimitochondrial antibodies in primary biliary cirrhosis.

In the last decade, the cloning and biochemical identification of mitochondrial autoantigens in primary biliary cirrhosis (PBC) as members of the 2-oxoacid dehydrogenase complex has greatly advanced the detection of antimitochondrial antibodies (AMA) and the understanding of the immunobiology of the disease. Here, we discuss the methods of detecting AMA and its isotypes, methods of epitope mapping, and using these methods in PBC liver immunohistochemistry and Ig gene usage. Increasing evidence, including the specific association of AMA with PBC, the unique similar but noncross-reactive conformational epitope of the lipoyl domains of the mitochondrial autoantigens, the specific binding of anti-PDC-E2 monoclonal antibodies and human combinatorial antibodies derived from PBC patients to the apical area of bile duct epithelial cells in PBC livers, and Ig gene usage of AMA, suggests that AMA is not an epiphenomenon of the disease but plays a significant role in the pathogenesis of PBC.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1997

The role of T cells in primary biliary cirrhosis.

While fervently studied by several laboratories, the role of T cells in the pathogenesis of primary biliary cirrhosis (PBC) still remains a mystery. The studies concerning cell phenotype, antigen specificity, and major histocompatibility complex (MHC)-T-cell receptor (TCR) interaction gathered thus far all address important aspects of this intriguing conundrum. However, the lack of an animal model and the genetic diversity of the human population with PBC make this task even more difficult. The possibilities regarding immune therapy resulting from such studies are of great importance. Future work concerning the T-cell epitopes--for both the pyruvate dehydrogenase complex (PDC), its related mitochondrial autoantigens, and any as yet unidentified PBC-specific autoantigens--may provide valuable information with regard to disease therapy. In addition, knowledge with regard to TCR usage and MHC association will help to clarify the pathogenic mechanisms of this enigmatic disease.

Antigen-Presenting Cells↗

PubMed1997

Central neurocytoma arising within a mature cystic teratoma of the ovary.

Tumors of central nervous system elements are uncommon in cystic teratomas and tend to be derived from glial or primitive neuroectodermal cells. We describe the case of a 23-year-old woman with a central neurocytoma arising in an otherwise mature cystic teratoma of the ovary. Histologically, the neurocytoma was composed of collections of oligodendroglioma like cells in a fibrillary matrix. Cytologically the tumor was identical in appearance to central neurocytomas occurring within the adult brain. It expressed synaptophysin and neuron-specific enolase, confirming its neuronal lineage, but not glial fibrillary acidic protein. The site of the tumor recapitulated the typical location of neurocytomas adjacent to the lateral ventricle in that in abutted onto an ependyma-lined cyst within the teratoma. The patient remains well and free of tumor 1 year after cystectomy, in keeping with favorable follow-up data for surgically excised central neurocytomas within the brain.

Adult↗

PubMed1997

Blood transfusion in obstetrics and gynaecology.

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Blood Component Transfusion↗

PubMed1997

The yeast silent information regulator Sir4p anchors and partitions plasmids.

Circular plasmids containing telomeric TG1-3 arrays or the HMR E silencer segregate efficiently between dividing cells of the yeast Saccharomyces cerevisiae. Subtelomeric X repeats augment the TG1-3 partitioning activity by a process that requires the SIR2, SIR3, and SIR4 genes, which are also required for silencer-based partitioning. Here we show that targeting Sir4p to DNA directly via fusion to the bacterial repressor LexA confers efficient mitotic segregation to otherwise unstable plasmids. The Sir4p partitioning activity resides within a 300-amino-acid region (residues 950 to 1262) which precedes the coiled-coil dimerization motif at the extreme carboxy end of the protein. Using a topology-based assay, we demonstrate that the partitioning domain also retards the axial rotation of LexA operators in vivo. The anchoring and partitioning properties of LexA-Sir4p chimeras persist despite the loss of the endogenous SIR genes, indicating that these functions are intrinsic to Sir4p and not to a complex of Sir factors. In contrast, inactivation of the Sir4p-interacting protein Rap1p reduces partitioning by a LexA-Sir4p fusion. The data are consistent with a model in which the partitioning and anchoring domain of Sir4p (PAD4 domain) attaches to a nuclear component that divides symmetrically between cells at mitosis; DNA linked to Sir4p by LexA serves as a reporter of protein movement in these experiments. We infer that the segregation behavior of telomere- and silencer-based plasmids is, in part, a consequence of these Sir4p-mediated interactions. The assays presented herein illustrate two novel approaches to monitor the intracellular dynamics of nuclear proteins.

Bacterial Proteins↗

PubMed1997