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Biomedical subjects

A Sönnerborg

Publications and source records attributed to A Sönnerborg.

At least 127 records · Page 7Linked to original sources
PubMed1994

Serum hepatitis C virus RNA levels in chronic hepatitis C--importance for outcome of interferon alfa-2b treatment.

Sera from 39 out of 40 patients with chronic hepatitis C virus (HCV) infection who had been treated for 60 weeks with interferon alfa-2b proved initially HCV RNA positive by reversed transcriptase polymerase chain reaction (PCR). These patients were analysed for genotype and quantitatively for HCV RNA levels prior to treatment by using a competitive PCR method with colorimetric detection of the amplified products. HCV RNA levels were correlated to outcome of treatment, mode of acquisition, histology and HCV genotype. The median pretreatment HCV RNA level in sustained responders (n = 15) with eradication of the viremia and normalization of serum ALT levels lasting 24 weeks post treatment was significantly lower than that in the combined group of non-sustained responders (n = 9) and non-responders (n = 15), 2.52 x 10(5) vs 8.90 x 10(5) genome equivalents per ml serum, p < 0.0125, respectively. 10 out of 17 patients with HCV RNA levels lower than the median level (5.64 x 10(5) genome equivalents per ml serum) had a sustained response to interferon treatment versus only 5/22 with levels equal to or higher than the median level, p = 0.04. No significant pretreatment differences in median HCV RNA levels according to mode of acquisition, genotype, or liver histology prior to treatment were seen. It is concluded that a low pretreatment HCV RNA level seems to be indicative of a sustained response to interferon alfa-2b treatment, whereas a high level seems to be indicative of a non-sustained or non-response. In the individual patient, however, the levels varied widely irrespective of response category.

Adolescent↗
PubMed1994

High sustained response rate and clearance of viremia in chronic hepatitis C after treatment with interferon-alpha 2b for 60 weeks.

To evaluate the effect of prolonged interferon-alpha treatment on serum aminotransferase levels and hepatitis C virus RNA in serum, 40 patients with chronic hepatitis C virus infection were treated with 3 MU interferon-alpha 2b thrice weekly for 60 wk. Before treatment all patients had elevated serum ALT levels for at least 1 yr, antibodies to HCV by second-generation tests and liver histological findings consistent with chronic hepatitis C. Before treatment hepatitis C virus RNA was found in serum in 39 of 40 (97.5%) patients. Normalization of ALT levels at treatment cessation was seen in 24 of 40 (60%) patients, of whom 15 of 24 (62.5%) had sustained ALT responses up to 24 wk after treatment. At follow-up, 24 wk after treatment, hepatitis C virus RNA was cleared from serum in 17 of 40 (42.5%) patients, including all sustained responders, one nonsustained responder and one nonresponder. We conclude that 60 wk of treatment with interferon-alpha 2b seems to induce a high percentage of sustained response, which coincides with cessation of viral replication.

Adult↗
PubMed1993

Detection of hepatitis C virus (HCV) RNA by PCR related to HCV antibodies in serum and liver histology in Swedish blood donors.

Serum samples from 103 blood donors or patients with slightly increased serum levels of liver enzymes were tested for antibodies to hepatitis C virus (anti-HCV) using second generation tests and for HCV RNA by the polymerase chain reaction (PCR). PCR was in a nested configuration, using primer pairs from the 5'-nontranslated region. The anti-HCV antibody was found by enzyme linked immunosorbent assay (ELISA) in 93 patients. The anti-HCV confirmatory second generation recombinant immunoblot assay (RIBA) was positive in 44, indeterminate in 34 and negative in 25 subjects. Histopathological examination of the liver was carried out in 51 subjects. HCV RNA was detected in serum of 39/41 (95%) RIBA positive patients, and in 7/34 (21%) RIBA indeterminate subjects, but in none of the RIBA negative subjects. All but one of the PCR positive patients with a RIBA indeterminate pattern exhibited the C22 band. HCV RNA was found in the serum of all but one patients with chronic active or persistent hepatitis, but also in one RIBA positive subject with normal liver tissue. These results imply that most patients with antibodies to two or more HCV antigens by RIBA will have a chronic replicative HCV infection associated with viraemia. HCV viraemia can also be present in some patients, who have antibodies to only one HCV antigen particularly the C22 epitope.

Adult↗
PubMed1993

Immunoglobulin M reactivity towards the immunologically active region sp75 of the core protein of hepatitis C virus (HCV) in chronic HCV infection.

Serum samples from a cohort of patients with chronic hepatitis C virus (HCV) infection were assayed for IgM anti-HCV/core reactivity with a "site-specific" ELISA, in which the solid phase was charged with the synthetic polypeptide analogue corresponding to the first 75 amino acids of the HCV core antigen (sp75). Thirteen of 24 (54%) patients exhibited IgM anti-sp75 reactivity. Both high-titered (1/16,000-1/32,000) and low-titered (1/1,000-1/4,000) IgM anti-sp75 reactive sera were found. IgM anti-sp75 antibodies persisted in the circulation over a long period in patients with fluctuating abnormal ALT levels. There was a striking association between detection of specific IgM anti-sp75 reactivity and the presence of HCV RNA in serum. Thus 11 of 15 (73%) sera containing HCV RNA also contained IgM anti-sp75 antibodies, while none of the HCV RNA-negative sera were IgM anti-sp75 reactive. Five of 11 patients without detectable levels of specific IgM anti-sp75 antibodies had their ALT levels returned to normal within 8 months to 3 years. Furthermore, a significant correlation was noted between the specific IgM anti-sp75 titers and the concentration of total plasma IgM, indicating that the immunological active region sp75 within the capsid of HCV has the capacity to induce an IgM secretion, which constitutes a substantial portion of the total plasma IgM, in patients with chronic HCV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗
PubMed1993

Hepatitis C viral RNA titers in serum prior to, during, and after oral treatment with ribavirin for chronic hepatitis C.

Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection.

Administration, Oral↗
PubMed1993

Sequence analysis of selected regions of the env (V3 loop and gp41) and gag (p7) reading frames of Ethiopian human immunodeficiency virus type 1 strains.

Amplified polymerase chain reaction (PCR) products, corresponding to the V3 loop and gp41 of the env, and p7 of the gag region, from proviral DNA of several Ethiopian and Swedish HIV-1 strains were sequenced. Of the six amino acids (GPGRAF) that constitute the principal neutralizing determinant (PND) within the V3 loop, the Ethiopian isolates all showed two amino acid changes (GPGQTF). Four to five other substitutions were found in the amino acids flanking the PND. Substitution of alanine (A) for threonine (T) should result in a change in the predicted secondary structure, i.e., disappearance of a coil structure. Percentage similarity data on a stretch of 22 amino acids within the V3 loop showed a concordance of the Ethiopian HIV-1 isolates with the sequences of published macrophage-T-cell tropic HIV isolates. Additionally derived protein sequences in two other regions showed two common substitutions in p7 and one to two substitutions in gp41 compared to a recent consensus sequence. These changes are hitherto unique for the Ethiopian strains, and suggest the presence of a clustering of a divergent HIV-1 strain in Addis Ababa, Ethiopia.

Amino Acid Sequence↗
PubMed1993

The neurotoxin-like sequence of human immunodeficiency virus gp120: a comparison of sequence data from patients with and without neurological symptoms.

A region of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp 120 has been claimed previously to be homologous to parts of snake venom neurotoxins and rabies virus glycoprotein ("the neurotoxic loop"). We have determined DNA sequences directly from a polymerase chain reaction amplified fragment corresponding to this region of HIV-1 gp 120 and have translated these to protein sequences. This was performed with the prototype HIVSF2 isolate and several Swedish HIV-1 strains, which were precultivated from blood cells or cerebrospinal fluid (CSF) or were directly obtained from CSF cells of patients with and without neurological symptoms. The results show that there are sequence similarities between a short segment of gp120 of clinical HIV-1 strains and the neurotoxic loop. The strains of patients with neurological symptoms did not, however, show a genetic shift of their sequences towards a greater similarity to the sequences of snake venom neurotoxins and rabies virus glycoprotein as compared to the strains of asymptomatic individuals.

AIDS Dementia Complex↗
PubMed1993

Neutralizing antibody response during human immunodeficiency virus type 1 infection: type and group specificity and viral escape.

The paradox that group-specific neutralizing antibodies (NA) exist in the majority of human immunodeficiency virus type 1 (HIV-1)-infected patients, whereas the NA response against autologous HIV-1 virus isolates is highly type-specific, motivated us to study the type- and group-specific NA responses generated upon presentation of escape virus, and the viral epitopes involved in the escape. Patients with demonstrable escape virus all developed group-specific NA, which were detectable after a delay and disappeared prior to disease development. The sera tested inhibited the binding of recombinant soluble gp120IIIB to cell-associated CD4, but group-specific virus neutralization required binding of NA to HIV-1 prior to viral attachment to target cells. Consecutive escape virus isolates were tested for sensitivity to neutralization by heterologous sera. Only minor differences were demonstrated, suggesting that the majority of the change in neutralization sensitivity is driven by the selective pressure of type-specific NA. Furthermore, no differences were observed in sensitivity to neutralization by anti-carbohydrate neutralizing monoclonal antibodies or the lectin concanavalin A, indicating a conserved nature of certain carbohydrate neutralization epitopes during escape. Finally the V3 sequence of three sets of consecutive virus isolates were analysed revealing amino acid mutations in V3 sequences of all escape virus isolates. The biological significance of these variations was confirmed further by the demonstration of changes in sensitivity to neutralization by anti-V3 monoclonal antibodies. These results strongly suggest a participation of the NA response against the V3 loop in the immunoselection of escape virus.

Amino Acid Sequence↗
PubMed1993

Outcome of acute symptomatic non-A, non-B hepatitis: a 13-year follow-up study of hepatitis C virus markers.

Thirty-nine of 61 prospectively followed patients who had had acute non-A, non-B hepatitis in 1978 were clinically reexamined in 1991 and tested for antibodies to hepatitis C virus (anti-HCV) with a second generation ELISA and RIBA and for HCV RNA by PCR. Acute hepatitis C was diagnosed in stored sera from 1978 in 24 patients, who were found still to be anti-HCV positive in 1991, and 16 of them were also HCV RNA positive. The majority of anti-HCV positive patients with or without HCV RNA had elevated serum ALT levels 13 years after onset of their acute hepatitis C. After 13 years follow-up, 1.6% of the patients had died of end-stage liver disease, 8% of anti-HCV positive patients had histologically confirmed liver cirrhosis, 79% of anti-HCV positive patients were judged to have chronic infection, whereas 21% seemed to have recovered. To conclude, we found that a majority of our patients with acute symptomatic hepatitis C continued to be viraemic 13 years after onset of hepatitis C, and that all continued to be anti-HCV positive by second-generation ELISA.

Acute Disease↗
PubMed1992

Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds.

Human immunodeficiency virus type 1 (HIV-1) isolates of 8 Ethiopian and 8 Swedish untreated AIDS-patients were examined for their sensitivity to 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) and leukocyte-derived interferon-alpha (IFN-alpha). No significant difference in drug sensitivity was found between Ethiopian and Swedish isolates, which all were sensitive to AZT, ddI and IFN-alpha except for one Swedish isolate. This isolate exhibited a mutation at amino acid position 215. These results suggest that it should be possible to perform clinical trials in Ethiopia using the same dose regimens as in Sweden.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV-1-infected Ethiopian patients.

OBJECTIVE: To determine the relationship and occurrence of cell-free viraemia, free or immune-complexed p24-antigen and p24-antibody levels in blood from HIV-1-infected patients in Ethiopia. METHODS: Peripheral blood was obtained from 66 Ethiopian and 137 Swedish HIV-1-seropositive patients. Blood samples were analysed for free or immune-complex bound p24 antigen by enzyme-linked immunosorbent assay before and after acid hydrolysis of immune complexes for infectious virus in plasma and peripheral blood mononuclear cells (PBMC), and for p24-antibody levels. We compared the kinetics of viral replication of Ethiopian with Swedish isolates in vitro. RESULTS: Infectious virus was isolated from PBMC in 95% and from plasma in 81% of Ethiopian AIDS patients. In contrast, p24 antigen was detected in only 5% of AIDS patients from Ethiopia, compared with 76% of those from Sweden. p24-antibody levels were much higher and more persistent in Ethiopian than in Swedish subjects. The ratio between reverse transcriptase activity and p24 antigen was significantly higher in Ethiopian isolate culture than in those of the Swedish isolates. CONCLUSIONS: Our results show that relationships between viraemia, p24 antigenaemia and p24-antibody levels in HIV-1-infected Ethiopian patients differ from those found in comparable Swedish patients. This pattern may partly explain the differences seen in the natural course of HIV-1 infection in Ethiopia and Sweden.

Adult↗
PubMed1991

HIV in pregnant women and their offspring: evidence for late transmission.

To assess the role of maternal viraemia in vertical transmission of HIV and the extent to which viraemia occurs during the various stages of pregnancy, we have attempted to detect human immunodeficiency virus (HIV) in 44 pregnant HIV-1 infected women during 47 pregnancies (30 continued, 17 aborted) and in 30 children and 12 fetuses. Infectious HIV was detected at some time during pregnancy in 59% of women from plasma and in 83% from either peripheral blood mononuclear cells or plasma. HIV was not isolated from any of the newborn babies (0/27) at birth. The mothers had a significantly higher frequency of viraemia during pregnancy than their children had by 6 months of age (p = 0.002); by this time HIV was recovered from 5 (26%) of 19 infants. HIV was not detected by virus isolation, in-situ hybridisation, or polymerase chain reaction (PCR) in 10 fetuses; the other 2 fetuses were positive either by in-situ hybridisation or by PCR but neither result could be confirmed in a second organ or by the other methods of detection. The findings show that there is no consistent spread of HIV across the placenta during maternal viraemia, and indicate that in most cases transmission occurs close to or at delivery.

Female↗
PubMed1991

HIV-1 in Ethiopia: phylogenetic divergence from other HIV-1 strains.

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences. The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.

Base Sequence↗
PubMed1991

Detection of HIV-1 DNA and infectious virus in cerebrospinal fluid.

The polymerase chain reaction (PCR) and a virus culture technique were used to detect human immunodeficiency virus type 1 (HIV-1) DNA in cerebrospinal fluid (CSF) cells and infectious virus in cell-free CSF, respectively, of 28 HIV-1 seropositive homosexual men. Provirus was detected in 24 patients of whom 15 were also culture positive. One subject was virus culture positive but not PCR positive. Two asymptomatic HIV-1 seropositive persons and one individual with persistent generalized lymphadenopathy were negative by both techniques. All of four patients with overt neurological symptoms, but also 20 of 24 patients without such symptoms were PCR positive. The data indicate that viral replication is common, and that the vast majority of HIV-1-infected individuals harbor the virus DNA in CSF, during all stages of infection.

AIDS-Related Complex↗
PubMed1991

Interferon-alpha and tumor necrosis factor-alpha in serum of patients in various stages of HIV-1 infection.

Serum samples of 120 patients in different stages of chronic human immunodeficiency virus type 1 (HIV-1) infection, 11 patients with primary HIV-1 infection (PHI), and 49 HIV-1 seronegative homosexual men were analyzed for tumor necrosis factor-alpha (TNF-alpha), interferon-alpha (IFN-alpha), and HIV-1 p24 antigen. Increased levels of IFN-alpha and TNF-alpha were found in some, but not all, cases with PHI. During progressing disease IFN-alpha occurred in serum with increasing frequency and concentration. Raised levels of TNF-alpha were found in all stages of chronic infection, but were less common in patients with AIDS than were raised levels of IFN-alpha. The levels of the two substances were not correlated. There was a correlation between IFN-alpha, but not TNF-alpha, and the occurrence of HIV-1 p24 antigen in serum. These results suggest that IFN-alpha and TNF-alpha are induced by different agents during HIV-1 infection. The findings would be consistent with the hypothesis that IFN-alpha and TNF-alpha are counteracting forces that have important down- and upregulatory effects, respectively, on HIV-1 replication in vivo.

Adult↗
PubMed1991

Combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine.

Patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who had p24 antigen despite treatment with zidovudine (AZT) for 4-28 months received 3 x 10(6) IU of native interferon-alpha (IFN-alpha) daily for 3 months. Infectious HIV was detected in the plasma of all patients, in most cases at high titers, before IFN-alpha treatment. There was no correlation between HIV titers and p24 antigen levels. Antiviral activity, as measured by significantly decreased levels of infectious virus or p24 antigen, was observed in six of eight completely treated but in only one of nine incompletely treated patients. After termination of IFN-alpha treatment, there was a significant rise of p24 antigen levels. During IFN treatment, absolute CD4 cell counts showed a tendency toward an increased rate of decline. The side effects were unexpectedly severe. Despite its anti-HIV effect in vivo, IFN-alpha in the dosages used does not seem to be a viable additional treatment for severely immunodeficient patients in ongoing AZT therapy.

Adult↗