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Biomedical subjects

E Penner

Publications and source records attributed to E Penner.

At least 37 records · Page 2Linked to original sources
PubMed1996

Nuclear architecture and ultrastructural distribution of poly(ADP-ribosyl)transferase, a multifunctional enzyme.

A monospecific autoimmune serum for poly(ADP-ribosyl)transferase (pADPRT) was used to localise the enzyme in ultrastructural cellular compartments. We detected enzyme in mitochondria of HeLa and Sertoli cells. Within the nucleoplasm the enzyme concentration was positively correlated with the degree of chromatin condensation, with interchromatin spaces being virtually free of pADPRT. During spermatogenesis we observed a gradual increase of the chromatin associated pADPRT that parallelled chromatin condensation. The highest concentration was seen in the late stages of sperm differentiation, indicating the existence of a storage form in transcriptionally inactive nuclei. In nucleoli pADPRT is accumulated in foci within the dense fibrillar component. Such foci are seen in close spatial relationship to sites of nucleolar transcription as revealed by high resolution immunodetection of bromouridine uptake sites. It is suggested that nucleolar pADPRT plays a role in preribosome processing via the modification of nucleolus specific proteins that bind to nascent transcripts and hence indirectly regulates polymerase I activity. The persisting binding of pADPRT to ribonucleoproteins may explain the observed disperse enzyme distribution at lower concentrations in the granular component. The fibrillar centres seem to contain no pADPRT. We conclude that known compounds of fibrillar centres like polymerase I are unlikely candidates for modification via direct covalent ADP-ribosylation.

Animals↗
PubMed1996

[Characterization of inflammatory infiltrates in autoimmune cholangitis: an immunohistochemical study].

Autoimmune cholangitis is clinically characterized by cholestasis and serologically by the presence of antinuclear antibodies (ANA) and a lack of antimitochondrial antibodies (AMA). Morphologic characteristics are non suppurative bile duct destruction (NSBDD), ductopenia and occasionally granulomas. The aim of the study was to characterize the inflammatory infiltrate to find about the possible mechanism of bile duct destruction in AIC. Liver biopsy material of ten patients (9 female/1 male, mean age of 45,5 a) with the clinical and serologic features of AIC were evaluated morphologically for the presence of NSBDD, ductopenia and granulomas. The inflammatory infiltrate was characterized immunohistochemically using Ab against CD3 (pan T lymphocytes), OPD 4 (helper T lymphocytes and memory T lymphocytes), CD8 (cytotoxic T lymphocytes), GB4 (activated cytotoxic T lymphocytes), L26 (pan B lymphocytes), CD56 and CD57 (NK/K cells). Lymphocyte subsets were investigated with regard to quantity and distribution within liver tissue. For control ten cases of PBC were also investigated simultaneously. NSBDD was found in five, granulomas in three cases. Portal inflammation was seen in all cases. In 9 cases T cells outweighed B cells. GB4 positive activated cytotoxic T lymphocytes were found within bile duct epithelium in five cases. All these cases showed associated NSBDD. NK/K cells were seen infrequently. Similar findings were observed in the ten cases of PBC. We therefore conclude that bile duct destruction in AIC is mediated by activated cytotoxic T lymphocytes. AIC cannot be differentiated from PBC histologically or by immunomorphology.

Antibodies, Antinuclear↗
PubMed1996

Anti-gp210 antibodies in sera of patients with primary biliary cirrhosis. Identification of a 64 kD fragment of gp210 as a major epitope.

Patients with primary biliary cirrhosis (PBC) frequently produce autoantibodies against gp210, an integral glycoprotein of the nuclear pores. this protein consists of three main domains: a large glycosylated lumenal domain, a single hydrophobic transmembrane segment and a short cytoplasmic tail. It has been previously shown that autoantibodies from PBC patients exclusively react with the cytoplasmic tail when recombinant rat gp210 expressed in Escherichia coli was used as antigen. Using human gp210 isolated from HeLa cells we found the lumenal domain as the major target. The aim of this study was to further characterize the dominant autoepitopes of gp210. Sera from 88 patients with autoimmune liver disease and 20 controls were used. Gp210 protein was digested with papain or endoglycosidase H and then subjected to immunoblotting. Autoantibodies against gp210 were detected in 12 of 43 (28%) PBC patients, but in none of the autoimmune hepatitis and control sera. Four of 12 (33%) anti-gp210 positive sera reacted with a fragment consisting of the cytoplasmic tail and 8 (66%) sera targeted an epitope located within the large lumenal domain. Furthermore, our data show that antigenic determinant is restricted to the 64 kD glycosylated amino-terminal fragment and that carbohydrate residues are an essential part of this novel epitope. We suggest that antigens possessing both epitopes namely; the glycosylated lumenal domain and the cytoplasmic tail should be used for screening tests in order to detect all sera with anti-gp210 specificity.

Animals↗
PubMed1995

Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210.

Patients with primary biliary cirrhosis frequently develop autoantibodies directed to gp210, a major glycoprotein of the nuclear pore complex. This protein contains a large glycosylated cisternal domain, a single transmembrane segment, and a short cytoplasmic tail. It has been previously shown that autoantibodies from primary biliary cirrhosis patients exclusively react with the cytoplasmic tail. We demonstrate that autoantibodies against gp210 recognize at least two different epitopes. 4 out of 12 anti-gp210 positive sera reacted with the fragment consisting of the cytoplasmic tail, and 8 sera targeted a novel epitope located within the large glycosylated lumenal domain. Moreover, our data prove that carbohydrate moieties are an essential part of this novel epitope. We propose, therefore, that future screening assays should be performed with antigens possessing both epitopes to detect all sera with anti-gp210 specificity.

Antibody Specificity↗
PubMed1995

Manifestation late in life of idiopathic adulthood ductopenia.

Idiopathic adulthood ductopenia is a chronic cholestasic liver disease of unknown etiology characterized by the loss of interlobular bile ducts. We describe three patients who fulfilled the diagnostic criteria of idiopathic adulthood ductopenia, but differed from the cases reported so far in late manifestation of the disease and a benign clinical course despite histologic evidence of ongoing cholangitis. Treatment with ursodeoxycholic acid in one patient resulted in improvement of biochemical markers of cholestasis, suggesting that chronic cholestasis in idiopathic adulthood ductopenia can be influenced beneficially.

Aged↗
PubMed1995

Screening for celiac disease in first-degree relatives of patients with celiac disease by lactulose/mannitol test.

OBJECTIVES: In first-degree relatives of celiac patients, the risk of oligosymptomatic celiac disease is elevated. These individuals therefore also have a higher potential for malignancy or nutritional deficiencies. Lactulose/mannitol permeability is increased in untreated celiac patients and has been recommended to screen for celiac disease. We investigated the usefulness of a lactulose/mannitol home test kit for screening first-degree relatives home test kit for screening first-degree relatives of celiac patients. METHODS: The lactulose/mannitol test was performed at home by 111 first-degree relatives. These subjects received the test kit from celiac index patients, were instructed by an information sheet how to carry out the test, and were asked about their symptoms by questionnaire. When lactulose/mannitol permeability was abnormal, endomysial antibodies were tested by immunofluorescence. Any relatives with positive endomysial antibodies were then biopsied. To investigate the specificity of the lactulose/mannitol test for celiac disease, 40 patients with nonspecific gastrointestinal symptoms were tested. RESULTS: Lactulose/mannitol permeability was elevated in 34 (31%) relatives, but only nine (8%) of those relatives showed positive endomysial antibodies. Flat mucosa was found in all nine relatives after biopsy. The prevalence of celiac disease was much higher (42%) among 12 relatives who contacted the outpatient clinic themselves because of symptoms. Seventy-one percent of the remaining 21 relatives with elevated permeability demonstrated normal intestinal permeability at a control test within 1 yr. CONCLUSION: By combining the lactulose/mannitol test with endomysial antibody testing, we have developed a good strategy for use in screening for celiac disease among first-degree relatives.

Adolescent↗
PubMed1995

Screening for celiac disease: a prospective study on the value of noninvasive tests.

OBJECTIVE: Celiac disease is frequently diagnosed in patients with nonspecific abdominal symptoms. Therefore, highly sensitive, specific, and simple noninvasive screening tests are needed. METHODS: This study compared the usefulness of IgG- and IgA-antigliadin antibodies, IgA-endomysial antibodies, and intestinal permeability in diagnosing celiac disease in 102 adult patients with nonspecific abdominal symptoms. In addition, all patients underwent small bowel biopsy as a gold standard for the diagnosis of celiac disease. RESULTS: Forty-nine patients were ultimately diagnosed as having celiac disease because of flat mucosa. Flatulence and signs and symptoms dating back to childhood were more frequent and abdominal pain less frequent (p < 0.05) in celiac disease but were not helpful for screening. IgA-endomysial antibodies showed a sensitivity and specificity of 100%; an altered intestinal permeability had also a 100% sensitivity, but only 55% specificity. IgG- and IgA-antigliadin antibodies' sensitivity (73% and 82%, respectively) and specificity (74% and 83%, respectively) were much lower. Combining the two antigliadin antibodies did not significantly improve the sensitivity and specificity. CONCLUSIONS: Our data show the advantage of IgA-endomysial antibodies for screening of celiac disease except in the case of patients with IgA-deficiency or dermatitis herpetiformis. In these patients, the permeability test could improve noninvasive differential diagnosis.

Adult↗
PubMed1995

Autoantibodies against constituents of nuclear pore complexes in patients with primary biliary cirrhosis and autoimmune hepatitis.

Sera obtained from patients with autoimmune liver disease were screened in indirect immunofluorescence microscopy for the presence of autoantibodies. Patients' sera, which strongly stained nuclei (ANA) with peripheral accentuation, were used for further experiments to define the corresponding antigen(s). Nuclei and nuclear subfractions were isolated from HeLaS3 cells and used as antigen source. Immunoblotting experiments were performed after separation of nuclear proteins by one- and two-dimensional polyacrylamide gel electrophoresis. Some ANA positive sera recognized the nuclear protein with molecular mass of approximately 200 kDa. Further analysis revealed that the patients' sera reacted with gp210, an integral protein of the nuclear pores. The incidence and clinical significance of these antibodies is discussed.

Autoantibodies↗
PubMed1993

Antinuclear antibody profile in UCD line 200 chickens: a model for progressive systemic sclerosis.

The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are fully established, only scarce data are available on the dynamics and clinical significance of autoantibodies in the very early stages of this systemic fibrotic disease. The University of California at Davis line 200 (UCD 200) of chickens spontaneously develop a PSS-like disorder with an acute inflammatory stage around 60 days after hatching, leading to fibrosis with fast progression. In order to address a possible correlation between the occurrence and titer of autoantibodies and the initial disease activity, we have chronologically investigated the presence and titer of autoantibodies directed against several human nuclear antigens in this animal strain. In UCD-200 chickens, we found a progressive increase in autoantibodies to histones, to ssDNA and--to a lesser degree--dsDNA with peaks at the age of 60 and 120 days, to poly(I) and poly(G) with a peak at 120 days and an elevation in anti-cardiolipin antibodies. Total immunoglobulin concentrations, anti-Ro, anti-La and anti-Sm showed no significant differences as compared to negative results in healthy normal controls. Our data reveal parallels in the antinuclear antibody (ANA) spectrum between UCD-200 chickens and human autoimmune collagen diseases, but do not reflect the typical ANA spectrum found in the foudroyant form of diffuse scleroderma.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Nucleolar proteins B23 and C23 as target antigens in chronic graft-versus-host disease.

Previously we observed that sera from recipients of allogeneic bone marrow transplants who developed extensive chronic graft-versus-host disease (GVHD) intensively stained the nucleolar region of target cells in indirect immunofluorescence microscopy. To identify the target antigens, immunoblotting experiments were performed using isolated nuclei, isolated nucleoli, and purified nuclear and nucleolar proteins as the antigen source. The nucleolar phosphoproteins B23 and C23 were identified as the main target antigens. Eleven of 19 extensive chronic GVHD sera reacted with these nucleolar phosphoproteins. In addition, four sera recognized histone H1, and two sera recognized the nuclear lamins A and C. Our patients reacting with the nucleolar proteins had symptoms resembling that of scleroderma or Sjögren's syndrome.

Antigens↗
PubMed1992

A lipoyl synthetic octadecapeptide of dihydrolipoamide acetyltransferase specifically recognized by anti-M2 autoantibodies in primary biliary cirrhosis.

Close to 95% of patients with established clinical, biochemical and histologic features of primary biliary cirrhosis (PBC) possess antimitochondrial M2 antibodies reacting with the E2 component, dihydrolipoamide acetyltransferase, of the pyruvate dehydrogenase complex. We examined the ability of synthetic peptides of E2 to be recognized in ELISA by sera from patients with PBC and autoimmune-related disorders. Sera from 14 PBC M2+ patients, 1 PBC M2- patient, 5 non-PBC M2+ patients, and 6 patients with chronic active hepatitis were studied. Among the seven E2 synthetic peptides tested (namely peptides 87-119, 167-184, 169-202, 267-302, 456-477, 498-513 and 530-543), only peptide 167-184 used as OVA conjugate and prepared with lipoic acid (LA) located on lysine 173 (natural inner lipoyl-binding site) was recognized in direct ELISA by PBC M2+ sera. The conjugated peptide 167-184 LA was not recognized in direct ELISA by non-PBC M2+ sera or by sera from patients with chronic active hepatitis. The free peptide 167-184 LA inhibited the ELISA reaction of PBC antibodies to PDH and totally abolished the typical immunofluorescence reaction of PBC sera on rat kidney, stomach and liver, or human HEp-2 cell substrates. No inhibition of ELISA or immunofluorescence reaction was found with the other E2 fragments including peptide 167-184 without LA. Our results show that the lipoyl moiety forms an integral part of a dominant conformational epitope recognized by PBC sera. Inasmuch as the peptide 167-184 LA was not recognized by non-PBC sera in direct ELISA, it could be used as a valuable probe for PBC diagnosis.

Acetyltransferases↗
PubMed1991

[Experiences with liver transplantation in hepatitis B antigen positive liver cirrhosis].

From 1982 to January 1991 228 orthotopic liver transplantations (OLT) were performed in 213 patients with end-stage disease at the Vienna transplantation centre, 1st University Department of Surgery. 14 patients were serum HBV surface antigen (HBsAg) positive at the time of transplantation. In the first 4 patients only OLT was performed; postoperatively all grafts became reinfected and the patients developed chronic hepatitis. In a further series, immunoprophylaxis against hepatitis B virus reinfection was carried out with hyperimmuneglobulin. In 4 patients short-term immunoprophylaxis was performed; all of them were seronegative after OLT, but HBsAg ++reoccurred in the serum within 3-16 weeks after transplantation and all patients experienced reinfection of their graft. The 2 patients, who had been transplanted in a replicative state (HBeAg positive) showed a fatal course of hepatitis in the graft. Out of 6 patients given long-term immunoprophylaxis 3 cases showed stable liver function, without any signs of reinfection, and the HBsAg negative status remained for up to 19 months after transplantation. Since two patients displayed a HBV replicate status prior to transplantation, alpha interferon was administered preoperatively, which resulted in decreased serum HBV-DNA levels.

Adult↗
PubMed1990

Autoantibodies against different histone H1 subtypes in systemic lupus erythematosus sera.

The H1 histones represent the most heterogenous class of histone proteins. In this study, we analyzed the specificity of human antibodies against 6 H1 subtypes. H1 histones from rat organs were separated by reverse-phase high performance liquid chromatography and used as antigens in immunoblotting experiments. Sera containing anti-histone H1 antibodies were obtained from patients with systemic lupus erythematosus. Of the 9 sera tested, 2 reacted with only 1 H1 subtype. The other sera recognized different combinations of H1 subtypes. Only 1 serum reacted with all 6 H1 subtypes. Histones H1.5 and H1.1 were the subtypes most frequently recognized by the human autoantibodies. Our data indicate that human anti-H1 antibodies represent a heterogenous population, directed mainly against epitopes localized in the variable region of the H1 molecule.

Antibody Specificity↗
PubMed1990

Antibodies to nuclear lamin C in chronic hepatitis delta virus infection.

Sera of patients with chronic hepatitis delta virus infection stained the nuclear periphery in indirect immunofluorescence. Using proteins of isolated nuclei, isolated nuclear matrices, the nuclear pore complex-lamina fraction and purified lamins A and C as antigen source in immunoblotting experiments, nuclear lamin C was identified as the reactive antigen. Most sera tested (8 of 10) recognized nuclear lamin C exclusively, but not the nuclear lamins A and B. Antibodies reacting with both nuclear lamins A and C, which share extensive sequence homologies, have been reported to occur in autoimmune hepatitis and primary biliary cirrhosis. The present findings suggest that the novel autoantibody associated with chronic hepatitis delta virus infection recognizes an epitope localized in the short carboxyterminal region of nuclear lamin C.

Antibodies, Antinuclear↗
PubMed1990

Identification of the platelet glycoprotein IIb/IIIa complex as a target antigen in primary biliary cirrhosis-associated autoimmune thrombocytopenia. Evidence that platelet-reactive autoantibodies can also bind to the mitochondrial antigen M2.

A 67-year-old woman with a 4-year history of primary biliary cirrhosis (PBC) unexpectedly developed autoimmune thrombocytopenia. The platelet-bound IgG antibody was eluted from the patient's platelets to determine the platelet target antigen. The autoantibodies were found to precipitate the platelet glycoprotein complex IIb/IIIa of autologous and allogeneic platelets. A further precipitate of 70 kDa was detectable under reducing conditions. In addition, platelet-reactive antibodies bound to the 70 kDa mitochondrial antigen M2. No cross-absorption studies were performed to confirm that a single antibody reacted with both antigens. Computer analysis of published peptide sequences of the mitochondrial protein and the platelet GPIIb/IIIa complex showed partial amino acid sequence homology suggesting the possibility of a common antibody binding site. These findings suggest a relationship between the development of autoimmune thrombocytopenia in PBC and the underlying liver disease.

Aged↗
PubMed1990

A recombinant topoisomerase I used for autoantibody detection in sera from patients with systemic sclerosis.

We report the expression of a cDNA clone encoding 695 carboxyl-terminal amino acids of human DNA topoisomerase I (topoI) in Escherichia coli. More than 96% of the anti-HeLa topoI-positive sera from patients with a connective tissue disease displayed also an immunoreactivity with this recombinant protein (the HTopoA protein). Sera from patients with a definite diagnosis systemic sclerosis and reacting with HeLa topoI, all reacted with the HTopoA protein as well. Sera from patients with systemic sclerosis that did not contain anti-topoI antibodies (about 30% of the systemic sclerosis sera), as concluded from HeLa immunoblot, displayed also no immunoreactivity with our recombinant antigen. By expressing different fragments of HTopoA, we were able to assign at least three different autoimmune epitope regions on the HTopoA protein and we show that over a period of 5 years the amount of anti-topoI antibodies against these regions may fluctuate.

Amino Acid Sequence↗
PubMed1990

Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies.

Sera from 32 bone marrow allograft recipients were screened for the presence of autoantibodies 4-61 months post-graft. Sera from 12 of 19 patients with extensive chronic graft-versus-host disease (c-GVHD) stained the nucleolar region strongly in immunofluorescence, indicating the presence of specific antinucleolar antibodies. In contrast, none of three patients with limited and none of 10 patients without c-GVHD had antinucleolar antibodies. Antibodies reacting with nuclear constituents other than nucleoli were found in five of the 12 antinucleolar positive patients. The appearance of antinucleolar antibodies coincided with early clinical symptoms of c-GVHD. We conclude that the appearance of antinucleolar antibodies after bone marrow transplantation is specific for patients with extensive c-GVHD. Furthermore, the development of extensive c-GVHD is paralleled by the emergence of these antinucleolar antibodies.

Adolescent↗