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R Seelig

Publications and source records attributed to R Seelig.

At least 37 records · Page 2Linked to original sources

[A hepatitis non-A, non-B-associated substance in the feces--identification and cloning of a partially double-stranded circular DNA].

By means of a radioimmunoassay a substance excreted in feces could be detected in patients with hepatitis non-A,non-B (HNANB). Feces extracts of patients with sporadic and posttransfusion HNANB as well as of healthy persons were precipitated with PEG, digested with RNase and DNase and separated on CsCl. In HNANB-patients a RIA-positive material with a density of 1.3 g/ml CsCl could be detected which contained a partially double-stranded circular DNA. Cloning of this DNA in lambda-phase resulted in DNA of about 5 Kb, which hybridized with feces DNA under stringent conditions. The 5 Kb-DNA were mapped with different restriction enzymes. A 1.5 Kb EcoRi-fragment cross-hybridizes with HBV-DNA. No hybridization and sequence homologies were found with human, viral and procaryotic DNA as well as with plasmid and phage DNA (data base EMBL, Heidelberg). It is assumed that the DNA excreted in feces of HNANB-patients represents a viral genome not detected so far.

Cloning, Molecular↗

[Hepatitis non-A, non-B-associated substance in stool from patients with posttransfusion and sporadic hepatitis].

A hepatitis non-A,non-B-associated substance (HNANB-AS) excreted in feces has been detected by means of a sandwich radioimmunoassay using reconvalescent serum and IgG from patients with posttransfusion HNANB. 4380 stool filtrates from 1599 patients were screened with this assay. In patients with posttransfusion or sporadic acute and chronic HNANB the substance was detected with a mean frequency of 34%, in acute posttransfusion HNANB, where samples were screened at the beginning of the clinical symptoms, 71.4% of stool specimens were positive for HNANB-AS. A high frequency of positive results was found in patients undergoing dialysis (31.3%), hemophiliacs (16.6%) and patients with cryptogenic cirrhosis (16%). Positive specimens were seen in hepatitis A (7.1%), acute and chronic HBV-infection (9.6%), various liver diseases (7.8%), outpatients of a physician (3.1%) and clinical or laboratory staff (6%). In these groups, too, anamnestic data speaking in favour for a possible HNANB frequently were obtained. The discovery of a partially double-stranded circular DNA of 5.0 Kb in HNANB-AS which sequence differs from human, bacterial and known viral DNA, argues the presence of a viral particle in stools of patients with sporadic and parenteral HNANB.

Acute Disease↗

[Hepatitis non-A, non-B-associated DNA--demonstration of DNA in proven infectious anti-D-immunoglobulin].

An anti-D-immunoglobulin preparation implicated in a hepatitis non-A,non-B transmission was analyzed for the presence of a DNA, which was originally isolated, cloned and sequenced from feces of a patient with posttransfusion HNANB. The investigation was performed by a DNA polymerase chain reaction using synthetic oligoprimers. Commercially available immunoglobulin preparations served as controls. The demonstration of identical DNA sequences in the infectious material speaks in favour of this up to now unknown circular and partially double-stranded DNA to be a virus genome involved in hepatitis non-A,non-B.

Antibodies, Anti-Idiotypic↗

Vertebral erosions in patients undergoing maintenance hemodialysis for chronic renal failure.

Unlike articular erosions in the appendicular skeleton, the frequency, appearance, and clinical relevance of vertebral erosions in azotemic osteodystrophy are not known. Lateral vertebral radiographs of 118 patients on maintenance hemodialysis were reviewed to assess the frequency, distribution, and rate of progression of vertebral erosions. Thirty (25%) of 118 patients showed a superficial corner erosion resembling the so-called Romanus lesion of ankylosing spondylitis. Their presence, whether at a single level or at multiple levels, did not correlate with erosive changes in the phalanges or sacroiliac joints that are known to occur in renal osteodystrophy. Vertebral erosions may progress slowly with time, but seem to have limited bearing on clinical symptoms. In two patients, however, the radiographic changes progressed dramatically, simulating an infection. Biopsy and surgical intervention were considered but not carried out because one patient declined and in the other an infected graft was identified as the source of infection. Both patients had negative scintiscans, and their subsequent clinical courses excluded infectious spondylitis. Vertebral erosions in patients on maintenance hemodialysis are frequent, and there appears to be a spectrum of changes from superficial erosions to large resorptive defects. Further diagnostic evaluation of these erosive changes appears to be warranted only rarely.

Adult↗

Determinants of plasma beta 2 microglobulin concentration: possible relation to membrane biocompatibility.

Beta 2 microglobulin (beta 2m) concentrations were measured by radioimmunoassay in the serum of haemodialysed patients. beta 2m was higher in males (n = 48) than in females (n = 26), i.e. 40.3 +/- 10.1 mg/l (SD) vs 31.2 +/- 8.0, P less than 0.01). beta 2m was not significantly higher in patients with bone cysts (37.7 +/- 11.4 mg/l vs 37.0 +/- 10.0), but median duration of dialysis was significantly (P less than 0.01) longer in patients with bone cysts (90 vs 57 months). beta 2m was lower in patients maintained on dialysis for less than 1 year and whose residual urine volume was greater than 0.1 litre per day. During one single session of dialysis, using cuprophane membranes, beta 2m increased acutely at 15 min and had risen by 32.4% at the end of the dialysis session, more than could be explained by haemoconcentration. In contrast, beta 2m acutely decreased by 38.7% during a single session using polysulphone membranes and the steady state predialysis values were lower by 37.1% after two weeks intermittent haemodialysis with polysulphone membranes. After re-exposure to cuprophane serum beta 2m increased to the original value. It is concluded that beta 2m concentrations on dialysis are a function of residual urinary volume, sex, and type of membrane used. Data are consistent with effective removal of beta 2m by membranes with high cut-off.

Biocompatible Materials↗

[Diagnostic significance of the detection of hepatitis B virus DNA in acute and chronic hepatitis].

1065 sera from patients with acute and chronic hepatitis-B-virus-(HBV-) infections, double infections (HBV, HAV, nonA-nonB, delta-Ag) as well as patients with HBs-Ag-negative hepatitis (HAV, nonA-nonB) and healthy subjects were investigated for the presence of hepatitis-B-virus-DNA using molecular hybridisation. The sensitivity of the method was 0.1 pg HBV-DNA/100 microliters. HBV-DNA could be detected in 62% of cases of HBs-Ag-positive sera with HBe-Ag, in 8.9% with anti-HBe and in 11% of e-marker free sera. In acute hepatitis HBV-DNA was present in 44%, in chronic hepatitis in 71% of HBe-Ag-positive sera. In HBs-Ag-negative sera containing only anti-HBc, HBV-DNA, depending on the anti-HBc-titre, was present in 13-24% of cases. HBV-DNA could not be detected in patients with HBV infections (anti-HBc and anti-HBs positive) in the past or in HBV-marker-negative hepatitis. Follow-up investigations on acute and chronic HBV-infections showed that the disappearance of HBV-DNA generally preceded the disappearance of HBe-antigen by about 2-3 weeks. In chronic hepatitis the time interval can amount to several months or years. Double infections with other hepatotropic viruses (nonA-nonB and delta-virus) can lead to a temporary suppression of HBV-DNA replication.

DNA, Viral↗

Cutaneous papulo-vesicular eruptions in non-A, non-B hepatitis.

A relapsing papulo-vesicular rash with or without pruritus was observed in 54 out of 148 patients (36%) with posttransfusion or sporadic, acute or chronic, non-A, non-B (NANB) hepatitis. The predominant location was the trunk and the anterior surfaces of the upper extremities. The face was affected less often. The eruptive phase was accompanied by general symptoms and increases in aminotransferases and gamma-GT values. The nature of the eruption was consistent with cutaneous reactions as frequently seen in enterovirus infections. No predominance was found for special groups of patients when the skin lesions were correlated to either sex, mode of infection or pattern of transaminase elevation (i.e. monophasic or bi-, and multi-phasic).

Acute Disease↗

Virus-binding activity of fibronectin: masking of hepatitis A virus.

Human plasma fibronectin interacts with viruses. When fibronectin-containing human sera negative for antibodies to hepatitis A virus (HAV) were added to suspensions of HAV, radioimmunological detection of HAV was reduced. This masking effect seemed to depend on the fibronectin concentration of the sera: plasma fibronectin purified by cryoprecipitation and affinity chromatography showed a masking effect on purified HAV which was dependent on the concentrations of fibronectin and HAV. Fibronectin peptides were obtained by subtilisin digestion: the non-collagen-binding regions of the fibronectin molecule were involved in the binding of HAV. We conclude that fibronectin has a virus-binding activity which interferes with radioimmunological methods for virus detection, and may contribute to the frequent transmission of hepatitis viruses by blood products enriched in fibronectin.

Adult↗

[Hepatitis non-A, non-B. Retro- and prospective studies on the epidemiology of the acute disease].

The epidemiology was studied in 159 consecutively admitted patients (1981-1983) with acute and chronic parenteral and non-parenteral type non A, non B hepatitis (HNANB). To establish the frequencies of types A (HAV), B (HBV) and HNANB data were collected from the official health statistic of the Federal Republic of Germany (1980-1982). Accordingly, 5 out of 100 000 persons acquired HNANB each year. There was no regional prevalence (i. e. industrial areas, cities) in HNANB as it was present in HAV. The relation of HNANB to HAV and HBV was 1:3:2,4 (health statistic), but was 1:1,1:3 in clinical studies (1979-1983, n = 2027). Of the patients with non-parenteral HNANB (n = 50) most were elder than 20 years of age. Susceptibility for parenteral acquired HNANB was observed in all groups of age. The evaluation of the possible modes of infection revealed 59% of the patients with non-parenteral ("sporadic") type HNANB, other 28,9% had posttransfusion HNANB. When monthly incidence was examined the HNANB infectivity of bloodtransfusions was high during May, June and October. Most cases of sporadic HNANB became clinically ill during summer and October. Difficulties in determination of incubation periods became evident because of the fluctuating increases and decreases of aminotransferases: In posttransfusion HNANB (n = 28) the first increases of aminotransferases were recorded at day 18 +/- 13 whereas peak values happened at day 77 +/- 21. It is concluded, that HNANB is an infection which affects a high proportion of the population, and needs consideration as a common infectious disease.

Adolescent↗

The cyclic behaviour of NANB hepatitis as basis for standardized diagnostic.

Efforts were made to characterize the clinical and biochemical behaviour of NANB hepatitis in 51 patients. 15 patients had posttransfusion NANB hepatitis, 36 a sporadic form of the disease. The patients' complaints predominantly were nausea and vomiting (64%), in about each 25% cardial complaints, lassitude, muscle pain and fever were observed. An eczema in a kind of maculopapular eruptions was frequently seen. The ratio of SGOT/SGPT was almost never less 1.0, Gamma-GT was consistently increased. The biochemical changes relapsed frequently. In posttransfusion NANB hepatitis the relapses were observed to occur predominantly around day 21, 28, 42, 49, 56, 63, 70, 77, and in further weekly intervals.

Alanine Transaminase↗

Detection of a non-A, non-B hepatitis associated substance in stools.

Investigation of stool samples (N = 2223) from 1377 persons revealed an antigen-like substance in the fecess of patients with clinically defined non-A, non-B hepatitis. Manifold investigation showed an intermittent excretion which correlated to the typical increases and decreases of transaminases in this disease. Positive results could be obtained by a randomized study in 30% of patients with NANB-hepatitis. Selected cases of sporadic and posttransfusion NANB-hepatitis showed an overall frequency of 50%. The test was predominantly negative in healthy persons and disease controls. The frequency of about 3% in fece cases was thought to be due to detection by chance.

Feces↗

Characterization of a non-A, non-B hepatitis associated substance in stools.

Using the 125J-labeled isolated IgG-fraction of reconvalescent sera from patients with NANB-hepatitis a radioimmunoassay for the detection of the NANB-hepatitis associated antigen in stool was established (RS). To characterize the antigen, stool suspensions of healthy persons and NANB-patients were analyzed by sedimentation on sucrose gradient (3-35%) before and after incubation of 125J-labeled normal IgG or IgG from reconvalescent patients. Stool was spiked with normal sera and with serum completely free from immunoglobulins. The antigen could be recovered in a fraction with similar sedimentation rate as IgG. Preincubation of Ag-positive stool with 125J-labeled IgG of reconvalescent serum resulted in a significantly higher sedimentation rate of the labeled IgG. The spiking of stool suspensions with serum of healthy donors and serum free of immunoglobulins resulted in a negative RIA-Test. The antigen could be absorbed on polystyrol beads preincubated with human serum of healthy donors. A positive test was achieved, however, only with the labeled IgG-fraction of reconvalescent serum and not with that of healthy donors. The results permit the following preliminary conclusions: The NANB associated antigen in stools which was detected by isolated IgG from reconvalescent sera shows no cross reactions with IgG of healthy donors, which excludes nonspecific binding to immunoglobulins. The sedimentation coefficient is in the range of 7s. Normal human sera may contain an antigen-masking substance, which inhibits its accessibility for specific antibodies. This may explain the well-known difficulties in establishing a valid radioimmunoassay for the detection of NANB-antigen or corresponding antibodies in the patient's sera.

Antigens, Viral↗

[The clinical behaviour of by immunology unique courses of NANB hepatitis (author's transl)].

By means of both immunohistology and immunodiffusion a number of 7 by definition from NANB hepatitis suffering patients were found to belong to an unique antigen-antibody system. These patients responded to NANB infection with certain similarities: 1. The course of the disease exhibited a phasic pattern since increases in SGPT activity were observed at days 47 +/-- 10, 76 +/- 14, 117 +/- 18 and 157 +/- 7. 2. Increases of Gamma-GT were found to exceed values as observed in HAV and HBV infection. Thus, Gamma-GT increases are incriminated as further characteristic of NANB hepatitis.

Alanine Transaminase↗

[Rational use of serological methods in diagnosis of virus hepatitis A and B (author's transl)].

The serological diagnosis of virus hepatitis A and B depends on the demonstration of the various virus antigens (HA-antigen, HBs-antigen, HBe-antigen) and on their corresponding antibodies (HA-, IgG- and IgM-antibody, HBc-antibody, Hbe-antibody and HBs-antibody). The knowledge of epidemiology of hepatitis and characteristic fluctuation of hepatitis-markers in the course of the disease allows not only statements on the aetiology, prognosis and the phase of hepatitis but also may help to avoid unnecessary expensive investigations and loss of time in diagnosis.

Antibodies, Viral↗

Antinuclear and pancreatic acinar cell antibodies in pancreatic diseases.

Recently, the presence of acinar cell antibodies (ACA) and antinuclear antibodies (ANA) in acute and/or chronic pancreatitis have been discussed in the light of an immunological pathogenesis of pancreatitis. In the present study sera of 109 patients with pancreatic diseases were scanned for ACA and ANA which were found in 5 of 16 patients, respectively. The frequency of ACA and ANA was similar in patients with pancreatitis of known and unknown aetiology. In conclusion, the presence of ACA and ANA seems to be rather an epiphenomenon than an index for a certain immunological aetiology of pancreatitis.

Adult↗