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G Norkrans

Publications and source records attributed to G Norkrans.

At least 73 records · Page 4Linked to original sources
PubMed1994

Genotyping of hepatitis C virus isolates by a modified polymerase chain reaction assay using type specific primers: epidemiological applications.

A polymerase chain reaction (PCR)-based assay using primers against the hepatitis C core gene has been described [Okamoto et al. (1992a): Journal of General Virology 73:673-679]. Within the two major HCV genotypes 1 and 2, the Okamoto system identifies two subtypes each (1a, 1b and 2a, 2b, respectively). Typing is achieved by a primary PCR with consensus primers followed by a nested PCR with type specific primers. The original assay was modified by addition of a parallel second PCR identifying the recently described major genotype 3. The assay also identifies in duplicate subtype 1b (type II by Okamoto), suggested to respond poorly to interferon. Reaction conditions were reviewed and melting temperatures of all typing primers equalised to increase strigency. The modified system functioned well and typing results were supported by partial core sequencing. The following distribution of genotypes was found in 53 hepatitis C virus (HCV) infected Swedish blood donors: genotype 1a (57%), 3 (19%), 1b (13%), and 2b (11%). In six recipients of HCV infected blood identified in a retrospective study, the recipient HCV genotype was identical to donor HCV genotype. Furthermore, in HCV positive couples identical genotype was observed when only one partner had an external risk factor; whereas genotypes were often diverse if both sex partners had parenteral risk factors. Finally, a cluster of hepatitis C cases in a haemodialysis unit was evaluated retrospectively. Eight patients had genotype 1b, two had mixed 1a and 1b, and one had type 1a. The modified HCV genotyping assay was of value in examining different epidemiological situations and can be expanded presumably to include future genotypes.

Base Sequence↗
PubMed1994

Tryptophan concentrations increase in cerebrospinal fluid and blood after zidovudine treatment in patients with HIV type 1 infection.

Cerebrospinal fluid (CSF) and blood concentrations of indoleamines and catecholamines were analyzed in 14 HIV-1-seropositive individuals before antiviral treatment with zidovudine, after 3-14 months of treatment, and, in 8 of the patients, also after 14-30 months. The median pretreatment concentrations of tryptophan in CSF and blood were low (224 ng/ml and 6.0 micrograms/ml, respectively), but an increase in these values by an average of 40% in CSF and 23% in blood was seen after 3-14 months of zidovudine treatment (p < 0.01) and remained undiminished after 14-30 months of treatment. No significant change was observed in the 5-hydroxytryptamine (5-HT, serotonin) level in blood or in the CSF concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite homovanillic acid (HVA). The CSF concentrations of the noradrenalin metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) had decreased by 12% on average (p < 0.01) by the time of the second follow-up, that is, after 14-30 months of zidovudine treatment. A decrease in neopterin during antiretroviral treatment correlated with an increase in tryptophan (p < 0.01). The data suggest that an association between decreased immune stimulation and reduced tryptophan degradation in patients treated with zidovudine.

Adult↗
PubMed1994

Histological outcome in patients with chronic hepatitis C given a 60-week interferon alfa-2b treatment course.

Forty patients with chronic hepatitis C virus (HCV) infection were treated with 3 MU interferon alfa-2b given subcutaneously for 60 weeks. A biochemical response with normalization of serum alanine aminotransferase (s-ALT) levels was seen in 24 patients (60%) at treatment cessation. A sustained response with continuously normal s-ALT levels during 24 weeks of follow up was seen in 15 of these 24 patients (62%), all of whom also became HCV RNA negative in serum. Histological changes in the pre- and posttreatment liver biopsies were assessed using a numerical scoring system. Biochemical responders had a significant decrease in all four scored categories: portal inflammation, piecemeal necrosis, spotty necrosis and fibrosis. Non-responders had a significant decrease in piecemeal necrosis and spotty necrosis, whereas the scores for portal inflammation and fibrosis remained unchanged. There was no significant difference in any of the scored categories in the pretreatment biopsy between responders and non-responders. We conclude that patients suffering from chronic HCV infection who responded biochemically and virologically to interferon treatment also improved their liver histology. Necroinflammatory activity decreased to some extent in biochemical non-responders, possibly giving them some benefit from the treatment, but not to the same extent as responders. No specific histological pretreatment findings were predictive of biochemical response to interferon treatment.

Alanine Transaminase↗
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

Markers of immune stimulation in the cerebrospinal fluid during HIV infection: a longitudinal study.

Markers of immune stimulation were studied in 76 sequential cerebrospinal fluid (CSF) samples from 19 patients infected with HIV-1 without antiretroviral treatment during observation periods ranging from 22 months to 6 years. Eight of these patients were further followed with 14 CSF samples for 3-24 months of zidovudine treatment. During the course of HIV-1 infection, the mean CSF neopterin and beta 2-microglobulin (beta 2M) concentrations increased from 12.7 to 20.4 nmol/l (p < 0.01) and from 1.93 to 2.17 mg/l (p < 0.05), respectively, while the mean peripheral CD4 + T cell count decreased from 624 to 320 cells x 10(6)/l (p < 0.001). The IgG index, reflecting intrathecal immunoglobulin production, increased from 0.72 to 0.92 (p = 0.08). The number of patients with CSF pleocytosis did not change significantly during follow-up (8/19 at baseline, 7/19 at endpoint). In the 8 patients followed up during antiretroviral treatment, a significant reduction in mean CSF levels of neopterin and beta 2M (-48% and -32%, respectively, p < 0.01) was seen after 3-12 months on zidovudine. We suggest that gradual increase in immune stimulation reflected by the rising CSF concentrations of neopterin and beta 2M indicates that HIV-1 infection in the central nervous system is progressive even in neurologically asymptomatic stages.

Adult↗
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

V3 sequences of paired HIV-1 isolates from blood and cerebrospinal fluid cluster according to host and show variation related to the clinical stage of disease.

The spread of HIV-1 to the nervous system occurs early during infection in a large number of asymptomatic virus carriers. In order to address the question whether the brain is targeted by a group of HIV-1 variants with increased neurotropic properties we have obtained 20 paired isolates from the blood and cerebrospinal fluid (CSF) of patients with varying severity of HIV-1 infection. We determined the nucleotide sequence of variable region 3 (V3) of the gp 120 envelope protein and studied the growth capacity of the virus isolates in primary monocyte/macrophage cultures. Blood and CSF V3 sequences could be grouped according to the host, whereas particular amino acid sequences related to tissue specificity were not identified. Moreover, the majority of HIV-1 isolates, independently of the tissue source, replicated in macrophage cultures. The isolates derived from the brain and blood compartments thus appeared genetically similar and could not be grouped according to their replicative capacities. The genetic distance between paired CSF and blood sequences was more pronounced in the group of patients with AIDS than in asymptomatic virus carriers. These observations indicate that the viruses present in the blood and CSF in the early stage of infection are genetically similar. Different mechanisms of adaptation or immunomodulation of the virus in CSF and blood may account for the increased intra-patient variability observed in the AIDS group.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Cerebrospinal fluid neopterin concentrations in central nervous system infection.

Cerebrospinal fluid (CSF) neopterin levels were determined by RIA in individuals with central nervous system (CNS) or human immunodeficiency virus (HIV) infections and in healthy controls. The mean CSF neopterin concentrations were 63.0 nmol/L in 15 patients with acute bacterial meningitis, 54.9 nmol/L in 15 patients with Lyme neuroborreliosis, 32.5 nmol/L in 10 patients with viral meningitis, 130.9 nmol/L in 8 patients with viral encephalitis, 13.9 nmol/L in 15 patients with asymptomatic HIV infection, 26.0 nmol/L in 11 patients with AIDS without dementia, 65.4 nmol/L in 4 patients with AIDS dementia, and 4.2 nmol/L in 24 healthy controls. Although patients with viral encephalitis had higher mean neopterin levels than any other patient category studied, the CSF neopterin concentrations cannot be used to discriminate between viral and bacterial infections. Analysis of CSF levels of neopterin may be useful as guidance in following clinical course and effect of treatment and can provide information of value in addition to CSF cell count as a measurement of CNS immune stimulation.

Adolescent↗
PubMed1993

Intestinal antibody responses to oral vaccination in HIV-infected individuals.

OBJECTIVE: To examine whether and at what stage mucosal immune responsiveness is impaired during HIV-1 infection. DESIGN: Intestinal and systemic antibody-secreting cell (ASC) responses were examined in eight HIV-1-infected volunteers and 10 seronegative control subjects after oral cholera and parenteral tetanus vaccinations. METHODS: ASC numbers were determined before and after booster vaccinations by the enzyme-linked immunospot (ELISPOT) technique. This technique was performed on cell suspensions obtained from enzymatically dispersed duodenal biopsies and from peripheral blood. RESULTS: Oral cholera vaccination evoked ASC responses in the intestinal mucosa of six out of eight HIV-1-infected volunteers, including patients with advanced disease and very low levels of circulating CD4+ T cells. The intestinal cholera ASC responses in HIV-infected volunteers were comparable to those in uninfected controls with regard to both magnitude and distribution of antibody classes. Most HIV-infected volunteers with only moderately reduced CD4+ T-cell counts also responded with vaccine-specific ASC in the blood, whereas none of the patients with < 200 x 10(6)/l CD4+ T cells per litre blood had detectable circulating ASC. CONCLUSION: These findings indicate that mucosal humoral immune responsiveness to a T-cell dependent antigen is maintained in HIV-infected individuals, despite concomitant systemic humoral hyporesponsiveness.

Administration, Oral↗
PubMed1993

Hepatitis B carriers in Sweden--effects of immigration.

The number of hepatitis B carriers in Gothenburg, the second largest city in Sweden, has gradually increased between 1980 and 1990. Altogether 525 chronic carriers (35% females) were found, corresponding to a prevalence of 0.11%. 401 (76%) were immigrants from high or medium prevalence regions, mainly the Middle East and Southeast Asia. 102 were native Swedes (19%). In 1988-90 the immigrants constituted 85% (154/182) of all new cases. 93% (245/264) of the carriers born in 1960-89 were immigrants, whereof 53% (130/245) were HBeAg positive. The increasing number of hepatitis B carriers in Sweden places demands on the public health service to undertake measures to prevent new cases of hepatitis B, as well as to discover and treat chronic liver disease induced by hepatitis B virus.

Adult↗
PubMed1993

Hepatitis C virus infection with progression to hepatocellular carcinoma: a report of five prospectively followed patients in Sweden.

Five Swedish patients with chronic hepatitis C were prospectively followed until hepatocellular carcinoma (HCC) developed. Hepatitis C virus (HCV) antibodies were analysed by a second generation anti-HCV ELISA and a recombinant immunoblot assay (RIBA-2) and viraemia by detection of serum HCV RNA by polymerase chain reaction. Four patients had post transfusion hepatitis and in one patient the source of infection was unknown. HCC developed after 8 to 23 years of mostly asymptomatic disease and all patients died. Four of them were repeatedly biopsied during follow-up and all had chronic active hepatitis. When HCC was diagnosed, cirrhosis was present in all 5. In 4 patients with available sera, anti-HCV was positive and confirmed with RIBA-2, whereof 2 were reactive only to the c-22 and c-33c epitopes. HCV-RNA was present in all sera when HCC was diagnosed. Thus, after prolonged disease duration these patients were still viraemic.

Adult↗
PubMed1992

Mother-to-infant transmission of hepatitis C virus.

OBJECTIVE: To describe the rate of perinatal transmission of hepatitis C virus (HCV). DESIGN: Follow-up study of newborn children of mothers with chronic HCV infection. SETTING: A university hospital in Sweden. PARTICIPANTS: Fourteen women with chronic HCV infection and their 21 newly born children. MAIN OUTCOME MEASURES: Detection of HCV RNA in serum by the polymerase chain reaction and detection of anti-HCV antibody by second generation assays. RESULTS: All mothers were found to be positive for anti-HCV antibody both by second-generation enzyme-linked immunosorbent assay (ELISA) and by second-generation recombinant immunoblot assay (RIBA-2); all also had detectable serum HCV RNA. Two children had long-lasting alanine aminotransferase (ALT) elevations, and one of them became HCV RNA positive. None of the other children developed biochemical hepatitis. However, two additional children had temporary viremia. Only the child with biochemical and biopsy-proven hepatitis and detectable HCV RNA in multiple blood samples actively produced anti-HCV antibody. CONCLUSIONS: Mother-to-infant transmission of HCV infection from chronically infected women without human immunodeficiency virus (HIV) infection seems to be uncommon.

Base Sequence↗
PubMed1992

Cerebrospinal fluid anti-cerebellar soluble lectin antibodies in human immunodeficiency virus type 1 infection.

Cerebrospinal fluid samples from 14 human immunodeficiency type 1 (HIV-1) seropositive patients in various stages of HIV infection were tested for the presence of autoantibodies to an endogenous manose-binding protein, the cerebellar soluble lectin (CSL), which has recently been found to be detected in a high proportion of patients with multiple sclerosis. An immunoblotting test was used with rat CSL as antigen. Seven patients were positive for anti-CSL and seven were negative. The seven anti-CSL-positive patients had signs of intrathecal immunoglobulin G production measured as an elevated IgG index, while the seven anti-CSL-negative patients had a normal IgG index. There was no apparent relation between infectious stage and the presence of anti-CSL. Immunological reactions such as anti-CSL autoantibodies may be a similar pathogenic mechanism in HIV and multiple sclerosis brain disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Lack of autologous neutralizing antibodies in the cerebrospinal fluid of HIV-1 infected individuals.

The cerebrospinal fluids (CSF) and sera from HIV-1-infected individuals at different clinical stages were monitored for neutralizing activity against CSF-derived HIV-1 isolates. None of the CSF samples and only one of seven serum samples could neutralize the autologous CSF isolate. CSF samples collected one to two years later from the same patients also lacked autologous neutralizing antibodies against these isolates. However, some CSF samples were able to neutralize heterologous CSF isolates albeit in low titers. HIV antibody positive control sera could readily neutralize all of the CSF isolates demonstrating that these isolates were not resistant to neutralization per se. IgG antibodies against the HIV-1 envelope protein and, specifically, against the V3 loop of HIV-1 gp120 (MN) were present in some CSF samples, although the samples lacked neutralizing activity. In summary, this study demonstrates a lack of autologous neutralizing antibodies in CSF samples when assayed against CSF-derived HIV-1 isolates.

Amino Acid Sequence↗
PubMed1992

Lymphocyte subsets and beta 2-microglobulin expression in chronic hepatitis C/non-A, non-B. Effects of interferon-alpha treatment.

Thirty-three patients with chronic hepatitis C/non-A, non-B were included in a randomized controlled study of interferon-alpha 2b (IFN-alpha 2b) treatment, 3 x 10(6) U three times weekly for 36 weeks. Using an immunoperoxidase technique, frozen liver biopsy specimens were examined with MoAbs for the presence of T helper cells (CD4), T suppressor/cytotoxic cells (CD8), total T cells (CD2) and B cells (CD22) before and after treatment. beta 2-microglobulin (beta 2-MG) expression on hepatocytes was semiquantified using a scoring system on sections from paraffin-embedded biopsy specimens. Serum levels of beta 2-MG were analysed with a radioimmunoassay technique. Intralobular T helper and T suppressor/cytotoxic cells declined significantly in the treated patients but not in the controls. The portal CD4/CD8 ratio did not change. Before treatment, serum beta 2-MG levels and hepatocyte beta 2-MG expression were significantly higher in patients with chronic active hepatitis compared to patients with chronic persistent hepatitis. Serum beta 2-MG levels increased significantly in responders during IFN treatment, with a maximum after 12 weeks. However, in the liver, the hepatocyte beta 2-MG expression was significantly decreased after treatment. Thus, IFN-alpha treatment does not seem to induce an increased HLA class I antigen hepatocyte expression in chronic non-A, non-B hepatitis, which favours the hypothesis that its anti-viral effects are more important in modulating the disease activity.

CD4-CD8 Ratio↗