Biomedical subjects

A Sönnerborg

Publications and source records attributed to A Sönnerborg.

At least 109 records · Page 6Linked to original sources

PubMed1995

Distinguishing acute from symptomatic chronic hepatitis C virus (HCV) infection by site-directed serology of the HCV structural proteins.

To distinguish acute from symptomatic chronic hepatitis C virus (HCV) infection, site-directed serology was done on the complete core, envelope 1, and envelope 2 proteins using multiple peptide assays. Serum samples were obtained from 7 patients with clinically confirmed acute HCV infections and from 36 patients with symptomatic chronic HCV infections. At onset of symptoms, all patients with acute infection had HCV RNA in serum, 1 had > 2 strong core peptide reactivities (A405 > 1.0), and the number of core reactivities increased with time in 6 patients. In contrast, 35 of 36 chronic-phase patients with HCV RNA in serum had 3-12 strong core reactivities (P < .001). Envelope 2 antibodies were found in 2 acute-phase and in 32 chronic-phase HCV patients (P < .01). Thus, a serum sample with HCV RNA from a patient with hepatitis can be classified as acute or chronic using site-directed serology of the HCV structural proteins.

Acute Disease↗

PubMed1995

Elevated levels of circulating tumor necrosis factor alpha in human immunodeficiency virus type 1-infected Africans living in Sweden.

Elevated levels of tumor necrosis factor alpha in serum were found in human immunodeficiency virus type 1 (HIV-1)-infected Africans to a higher extent than in matched HIV-1-infected Caucasians, both groups living in Sweden. The results suggest that factors not related to the environment contribute to enhanced synthesis of tumor necrosis factor alpha in HIV-1-infected patients.

Adolescent↗

PubMed1995

Levels of hepatitis C virus (HCV) RNA in serum and their relationship to levels of immunoglobulin M and G antibodies against HCV core protein.

The presence and levels of hepatitis C virus (HCV) RNA and immunoglobulin M (IgM) and IgG antibodies against the virus core protein were determined in 449 serum specimens. Despite the fact that a relationship between the presence, but not the levels, of HCV RNA and HCV IgM was observed, the significance of HCV core IgM assays seems limited.

Biomarkers↗

PubMed1995

Dynamic analysis of heterogeneous hepatitis C virus populations by direct solid-phase sequencing.

In the present study, we used a semiautomated solid-phase direct sequencing method to analyze sequence diversity and variation of the hypervariable E2/NS1 region in the hepatitis C virus (HCV) genome in isolates from patients seropositive for HCV. A total of 24 isolates of various origins were sequenced. Six of the patients, not subject to any antiviral therapy, were monitored longitudinally, and rapid sequence variations were observed over a period of 14 months. The nucleotide change rate was found to be 0.1 to 0.2 nucleotide substitution per genome site per year. Furthermore, isolates from five of the patients were used for a comparative study of the direct solid-phase sequencing approach versus the frequently used approach of sequencing individual reverse transcriptase PCR clones. The advantage of direct solid-phase sequencing for studying dynamic changes in heterogeneous populations of HCV is discussed.

Amino Acid Sequence↗

PubMed1995

Transmission of hepatitis C virus by transfusion in Orebro County, Sweden, 1990-1992.

A retrospective study of hepatitis C virus (HCV) transmission by transfusion was conducted in Orebro county. Out of the 7,900 active, registered blood donors, 21 repeatedly anti-HCV reactive (RIVA 2 positive or indeterminate) donors were diagnosed. Their 84 recipients from January 1990 through June 1992 were identified and 41 (49%) were alive in December 1992. A total of 13 anti-HCV reactive (RIBA 2 positive or indeterminate) were diagnosed in 39 investigated recipients. Of these 11 were previously undiagnosed, and seven were HCV RNA-positive. In the donor population 1.03% were anti-HCV-positive by ELISA, but only 0.09% were RIBA and HCV RNA-positive. In 1990, 0.06% of the blood components came from the HCV RNA-positive donors, and none during the first 6 months of 1992. In order to identify transfusion-transmitted HCV infections that took place before the introduction of tests for anti-HCV antibodies, patients with a history of transfusion and symptoms and signs of liver dysfunction or damage should be thoroughly tested.

Adult↗

PubMed1995

Two-year biochemical, virological, and histological follow-up in patients with chronic hepatitis C responding in a sustained fashion to interferon alfa-2b treatment.

Fourteen patients with chronic hepatitis C who had a sustained response to a 60-week interferon alfa-2b treatment course were followed, biochemically and virologically, 2 years after treatment cessation. Biopsies were repeated in 12 of 14 for histological and virological evaluation at 2-year follow-up. All 14 patients had normal serum alanine transaminase (s-ALT) levels and were negative for hepatitis C virus (HCV) RNA in serum during treatment and at short-term follow-up 6 months post-treatment. At 2-year follow-up, 13 patients still had normal ALT levels (< 0.6 mukat/L for women; < 0.8 mukat/L for men), 1 a near normal level (0.76 mukat/L); all were HCV RNA negative in serum, and 11 of 12 also in the liver. Liver histology improved during treatment and remained stable during the 2-year follow-up. The authors conclude that most sustained responders, who have normal ALT levels and are nonviremic at short-term follow-up 6 months after interferon treatment, will continue to have a durable long-term response without relapse of the viremia.

Adult↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

A total of 42 Swedish patients with biopsy-proven chronic hepatitis C virus (HCV) infection were treated with a natural human leucocyte alpha-interferon (HuIFN-alpha-Le), Alfanative (BioNative AB, Umeå, Sweden) in an open uncontrolled study. Two patients were withdrawn from treatment within 2 weeks due to non-compliance and were omitted from further analysis, and 40 patients (17 females), mean age 39 years (range 24-71) completed the study. All patients were HCV RNA-positive in serum prior to treatment, with raised alanine aminotransferase (ALT) levels > 1.5 times the upper normal limit known for more than 6 months. Interferon was given at a dose of 3 MU t.i.w. for an intended 24 weeks and follow-up was a further 24 weeks after treatment. Biochemical non-responders were withdrawn from treatment within 12-16 weeks but continued follow-up. Overall 21/40 (52.5%) patients had a complete biochemical response with normal ALT levels at the end of treatment. Sustained response during follow-up was seen in 8 (20%) whereas 13 (32.5%) had a non-sustained response. At the end of treatment 23 (58%) patients had undetectable serum HCV RNA and 9 (23%) at follow-up. Patients with sustained, non-sustained and non-response had a mean pretreatment HCV RNA level of 3.2 x 10(5), 2.5 x 10(6) and 3.2 x 10(6) genomes/ml, respectively, differences that did not reach statistical significance. Of the patients 3, 9, 10 and 14 had genotype 1b, 3a, 1a, and 2b, respectively, and 4 had mixed genotypes. Of the 23 patients with genotype 2b or 3a, 7 had a sustained response vs. none of the 13 patients with genotype 1a or 1b (p = 0.03). No patients with cirrhosis had a sustained response whereas 4/18 with chronic persistent and 4/18 with chronic active hepatitis had such a response. It is concluded that some 50% of patients treated with HuIFN-alpha-Le responded with normalisation of ALT levels but that only 20% had a durable response 24 weeks post-treatment, and that patients with genotypes 3a or 2b seem to respond better than patients with other genotypes.

Adult↗

PubMed1995

Efficacy of human leucocyte alpha-interferon treatment for chronic hepatitis C virus infection.

Adult↗

PubMed1995

Combination treatment with interferon alfa-2b and ribavirin for chronic hepatitis C in patients who have failed to achieve sustained response to interferon alone: Swedish experience.

BACKGROUND: Only 10-20% of patients treated with interferon alfa alone attain long-term benefits. More effective regimens are needed. METHODS: Twenty Swedish patients with chronic hepatitis C virus infection, ten with a prior non-response and ten with a non-sustained response to interferon alfa treatment alone, were treated with interferon alfa-2b and ribavirin in combination for 24 weeks, then followed up for another 24 weeks. Patients received interferon alfa-2b subcutaneously 3 MU thrice weekly and oral ribavirin 1000-1200 mg/day. RESULTS: All ten patients with a prior non-sustained response to interferon alone had a sustained biochemical response with normal aminotransferase levels at follow-up; nine also had a sustained viral response with a negative HCV-RNA test in serum. Among the ten patients with a prior biochemical non-response to interferon alone, five had normal aminotransferase levels at the end of therapy; four were negative for HCV RNA in serum. At follow-up, three had normal aminotransferase levels and a negative HCV-RNA test in serum. No major adverse effect was seen, apart from fatigue and an expected fall in hemoglobin levels from a mean of 155 g/l to 124 g/l at the end of therapy. All patients completed the treatment schedule, but the ribavirin dose was reduced in one patient because of a fall in hemoglobin to 99 g/l. CONCLUSIONS: These results indicate that combination treatment with interferon alfa-2b and ribavirin offers a chance of sustained biochemical response and virus eradication in a subset of patients who fail to achieve sustained response with interferon alfa alone.

Adult↗

PubMed1994

Rapid grouping of HIV-1 infection in subtypes A to E by V3 peptide serotyping and its relation to sequence analysis.

We developed a typing assay for HIV-1 using subtype specific peptides corresponding to the five major subtypes of HIV-1 (A to E). In eight patients serologically subtyped as A (n = 1), B (n = 3), C (n = 3) and E (n = 1) phyllogenetic analysis of sequenced V3 domain DNA completely correlated to the peptide serotyping. Out of 106 HIV-1 seropositive samples of a diverse geographical origin 88 (83%) could be subtyped by the peptide assay. Five were of subtype A, 33 of subtype B, 48 of subtype C, one of subtype D, and one was of subtype E. Swedish patients were mainly of HIV-1 subtype B and Ethiopian patients were mainly of subtype C, confirming the performance of the assay. Furthermore, subtype specific antibodies may persist up to nine years in HIV-1 infected patients though sera close to AIDS diagnosis may be difficult to type.

Africa↗

PubMed1994

A cell-binding Arg-Gly-Asp sequence is present in close proximity to the major linear antigenic region of HCV NS3.

By sequence analysis of the HCV NS3 protein we identified an Arg-Gly-Asp (RGD) motif, which is a known sequence for integrin-mediated cell adhesion, within a region of high hydrophilicity and surface probability. We therefore probed the complete NS3 protein for antigenic regions and cell binding activities using synthetic peptides. Antigenic regions were located to residues 1007-1022, 1047-1062, 1127-1142 and 1207-1232. The RGD-sequence reside two residues apart from the antigenic region at residues 1127-1142. Cell-adhesion experiments showed that NS3 peptides containing the RGD-sequence bound HUT-78 T-cells in a dose dependent manner. Antibodies to region 1127-1142 were found in all categories of HCV patients, arguing against the clinical significance of these antibodies. Extracellular NS3 proteins might disturb the migration of immune cells to the infected area by blocking the RGD-binding integrins, and thus, protect the infected cells.

Amino Acid Sequence↗

PubMed1994

Hepatitis C virus as a risk factor for the development of veno-occlusive disease of the liver.

Explore the source record for details and available documents.

Adult↗

PubMed1994

Colorimetric detection of competitive PCR products for quantification of hepatitis C viremia.

A method based on competitive polymerase chain reaction (PCR) and colorimetric detection of the amplified products was developed to quantify hepatitis C virus (HCV) genomes. Serum samples were obtained from patients who were treated with interferon alpha (IFN-alpha). After reverse transcription of the HCV RNA, the cDNA was coamplified with a serially diluted cloned HCV competitor DNA using nested PCR. The competitor DNA consisted of the amplified region of the wild type HCV cDNA with an internal region substituted with the lac operator (lacO) sequence. The PCR products were quantitated specifically by a colorimetric solid-phase assay. The results suggest that the method is well suited for analysing the kinetics of the anti-HCV effects during IFN-alpha treatment. The quantification assay is simple, reliable and suitable for quantitating HCV genomes in a large number of clinical samples.

Base Sequence↗

PubMed1994

Evidence of no change in V3 loop antibody recognition pattern in HIV type 1-infected Ethiopians between 1988 and 1993.

To determine the antibody reactivity against a V3 sequence based on local HIV-1 strains in Ethiopia, 635 serum samples derived in 1988 and 1993 were analyzed by peptide enzyme immunoassays. V3 peptides were produced according to the Ethiopian subtype C V3 consensus sequence (RKSIRIGPGQTFYAT), the HIV-1MN and HIV-1IIIB strains (subtype B), and the consensus sequences of subtypes A, D, and E. Initial analyses showed that Ethiopian anti-V3 positive sera cross-reacted between subtype A and subtype C peptides, and displayed much lower reactivities to the other peptides. Using inhibition experiments, it was found that the reactivities in the Ethiopian samples were specific for subtype C. A strong reactivity to the Ethiopian V3 consensus sequence was found in the majority of the Ethiopian samples (59%), independent of geographical origin or year of sampling. In Swedish HIV-1-positive sera, the high reactivities were restricted to the subtype B HIV-1MN peptide. A low prevalence (10%) of strong reactivity to the HIV-1MN V3 peptide was found among the Ethiopian samples. Using substitution peptide analogs it was found that a lack of cross-reactivity between subtype B and C peptides was dependent on the Arg-322 to Gln-322 substitution. The present data show that a similar antibody recognition pattern was present in sera sampled during 1993 as in sera sampled during 1988, suggesting that subtype C of HIV-1 has remained the dominant subtype in Ethiopia.

Amino Acid Sequence↗

PubMed1994

Antigenic structure of the hepatitis C virus envelope 2 protein.

The antigenic structure of the envelope 2 (e2) protein of the hepatitis C virus (HCV) was characterized by the use of 70 synthetic peptides and 131 human sera from persons with antibodies to HCV. Among 34 overlapping peptides spanning the e2 protein of HCV, two major antigenic regions were located to residues 484-499 and residues 554-569. The sequence of the two major antigenic regions of the e2 protein are partly well conserved within the described types of HCV. Both regions contain two Cys residues in close proximity, and the region at residues 554-569 contains a putative N-glycosylation site, which are factors that previously have been suggested to affect the immune recognition of the e2 protein. Using substitution peptide analogues where each position within residues 484-499 and 554-569 were sequentially substituted by Ala or Gly, the most essential residues for antibody binding were found to be the Pro-498, Ala-499, Ala-566, Pro-567, and Pro-568. All of these, except for the Pro-498 and Ala-566, are conserved among different HCV strains. Also, according to previous studies, position 496 often shows variations, which could be explained by position 496 being contained within the antigenic region at residues 484-499. Interestingly, none of the Cys residues at positions 486, 494, 564 and 569 were found to be essential for antibody binding, indicating that these are not essential in maintaining the e2 antigenicity of the peptides. In a material of 114 confirmed anti-HCV positive sera, derived from patients during the acute or the chronic phase of HCV infection, the prevalence of antibodies to the two major linear antigenic regions of the e2 protein was found to be 55% among HCV RNA-positive sera, and 53% among HCV RNA-negative sera. In conclusion, we have identified and characterized two major linear antigenic regions outside the two hypervariable regions of the e2 protein. Since these regions are accessible to the B cells of the infected host, these two regions are likely to be surface exposed either on the precursor polyprotein or the native e2 protein. Also, we could confirm that antibodies to the e2 protein co-exist with HCV viraemia.

Amino Acid Sequence↗

PubMed1994

Antigenic structure of the complete nonstructural (NS) 2 and 5 proteins of hepatitis C virus (HCV): anti-HCV NS2 and NS5 antibody reactivities in relation to HCV serotype, presence of HCV RNA, and acute HCV infection.

Antigenic regions within the nonstructural (NS) 2 and 5 proteins of hepatitis C virus (HCV) were identified and characterized by the use of 127 overlapping synthetic peptides and a serum panel consisting of 167 human serum samples from persons with antibodies to HCV. Initially, 20 anti-HCV-positive serum samples were used to screen the peptides covering the complete NS2 and NS5 proteins. Among the 27 overlapping peptides spanning the NS2 protein of HCV, only the peptide covering residues 960 to 975 was recognized by human sera. Within the 100 peptides covering the NS5 protein, major linear antigenic regions were located at residues 2284 to 2329 within the putative NS5a and at residues 2584 to 2599 and 2944 to 2959 within the putative NS5b. Additional minor linear antigenic regions were also identified within the NS5. The sequence of the antigenic region of the NS2 protein is, unlike most parts of the NS2 protein, highly conserved among the described types of HCV, whereas the sequence of the major antigenic region of NS5 shows variability among HCV types. The recognition of a peptide corresponding to a part of the major region of NS5 was found to be dependent on HCV type. In 129 anti-HCV-positive serum samples, the prevalence of antibodies to the NS2 protein was found to be 23% among HCV RNA-positive sera and 10% among HCV RNA-negative sera. In the same samples, reactivity to the major linear antigenic regions of HCV NS5 was found in 68% of the HCV RNA-positive sera and 67% of the HCV RNA-negative sera. Of 18 serum samples from five patients with acute HCV infections, and who seroconverted with respect to anti-HCV, 4 were found to be reactive to one or more of the 100 NS5 peptides and in three serum samples the NS5 reactivities were found to shorten the time for serodiagnosis of cross-reactive with a region form residues 2584 to 2599 of NS5, which has 67% homology with a six-residue sequence of NS2. In conclusion, in this study we have identified and evaluated the potential use of synthetic peptides corresponding to linear antigenic regions of the NS2 and NS5 proteins.

Acute Disease↗

PubMed1994

Hepatitis C virus replication in liver and peripheral blood mononuclear cells of interferon-alpha-treated and untreated patients with chronic hepatitis C.

Serum, liver tissue, and peripheral blood mononuclear cells (PBMC) were obtained from 72 patients with chronic hepatitis C, 19 of whom had received interferon-alpha (IFN-alpha) treatment. Hepatitis C virus (HCV) RNA was detected by polymerase chain reaction in the serum and liver of all patients with relapse after treatment and in 51 of 53 (96%) sera, 28 of 29 (97%) livers, and all of 13 (100%) PBMC from untreated patients but not in 3 patients with completely sustained responses. Minus-stranded HCV RNA was found in 5 of 14 (35%) sera, 16 of 17 (94%) livers, and 7 of 13 (53%) PBMC from untreated patients. The results indicate that HCV RNA is present not only in serum and liver but also in PBMC from the vast majority of untreated anti-HCV-seropositive patients and also in patients who respond to IFN-alpha treatment but then relapse. HCV replicates in the liver of almost all patients, but replication may possibly also occur in PBMC. By contrast, HCV RNA seems to be eradicated in patients with completely sustained responses.

Alanine Transaminase↗

PubMed1994

Variability of the E2/NS1 region of Swedish hepatitis C virus strains and its correlation to genotypes.

Serum RNA was extracted from 5 Swedish patients infected with hepatitis C virus (HCV). The N-terminal part of the genomic region coding for the gp70 (E2/NS1), including the hypervariable domain of the E2 protein, was reverse transcribed and amplified by the polymerase chain reaction (PCR) using biotinylated primers. The amplicon was immobilized on magnetic polystyrene beads coated with streptavidine. Solid-state sequencing was carried out on the bound single-stranded DNA, after denaturation. The results of phylogenetic sequence analysis and calculated ratios of transition and transversion mutations showed that 4 of the strains clustered together with the USA prototype strains HCV-1 and HCV-H (genotype I), while 1 strain was close to the Japanese isolate HCV-J, and particularly to isolate HCV-BK (genotype II). Possible antigenic epitopes in the Swedish strains were mapped in the HVR region.

Amino Acid Sequence↗