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Biomedical subjects

O Strannegård

Publications and source records attributed to O Strannegård.

At least 37 records · Page 2Linked to original sources
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

Persistent intrathecal immune activation in patients with herpes simplex encephalitis.

Neopterin and beta 2-microglobulin (beta 2M) levels were analyzed in sequential cerebrospinal fluid (CSF) and serum samples from 20 patients with herpes simplex encephalitis (HSE) and 30 patients with acute febrile encephalopathy of other cause (non-HSE). Markedly elevated acute phase CSF levels of neopterin and beta 2M were found in 19 HSE patients, but the levels were only moderately increased in most of those with non-HSE. Neopterin levels were analyzed in an additional 15 HSE patients who died within a month of the onset of neurologic symptoms and correlated with the clinical severity of the HSE. After HSE, but not after non-HSE, increased levels of neopterin and beta 2M persisted for a long time (> or = 13 years). Specific intrathecal IgG activity persisted in all but 2 HSE patients. These findings indicate that there is a vigorous acute inflammatory response and a long-term persistence of intrathecal cellular and humoral immune activity in HSE.

Adolescent↗
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

Detection of enteroviral RNA by polymerase chain reaction in faecal samples from patients with aseptic meningitis.

An assay based on the polymerase chain reaction (PCR) for detection of enteroviral RNA in stool samples was carried out using specimens from 74 patients with aseptic meningitis. The primer pair and probe were derived from the highly conserved 5' non-coding enterovirus genomic region. Enteroviral RNA was detected in faeces of all 36 patients in whom an enterovirus was isolated from stool. The PCR assay yielded positive results in additionally 3/6 cases where enterovirus diagnoses were obtained by virus isolation from cerebrospinal fluid and/or serological tests. Thus, the positive outcome of the PCR assay was 39 (93%) among the 42 patients with enterovirus diagnoses. Furthermore, 7/19 (37%) cases with an etiology that was not established by other means were positive in the test indicating that the PCR assay may give considerable additional etiological information in patients with aseptic meningitis. The limit of RNA detectability in the PCR assay was about 100 TCID50 when highly cytopathogenic enterovirus types (coxsackievirus type B5 and echovirus type 11) were tested. The PCR was negative in all 13 patients with non-enterovirus diagnoses except in one case with a herpes simplex virus type 2 infection. Since enterovirus-specific IgM antibodies could be detected in this case a dual infection seemed probable. All the negative controls, included in the study, were PCR-negative and no contamination was encountered. This study proves the usefulness of the PCR assay for detection of enteroviral RNA in stool samples and suggests that the test may be an alternative to virus isolation for rapid enterovirus diagnosis in patients with aseptic meningitis.

Adolescent↗
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↗
PubMed1992

Detection of enteroviruses in faeces by polymerase chain reaction.

A polymerase chain reaction (PCR) technique for the detection of human enteroviruses in stool specimens was developed. The test was based on the synthesis of cDNA, followed by PCR and slot blot hybridization. The primers used were selected from a highly conserved sequence in the 5'non-coding region of the enteroviral genome. By this method 27 different enterovirus serotypes (15 echo, 6 coxsackie A, 4 coxsackie B, poliovirus type 2 and enterovirus 71) from 89 patients could be detected. Using positive virus culture as reference, the sensitivity of PCR was 69% after 30 cycles of amplification, 91% using 30 + 10 cycles and 100% following 2 rounds of amplification with ensuing hybridization. None of 23 stool samples from healthy individuals or patients with meningitis of proven non-enteroviral etiology were positive by the PCR. By contrast, 13/26 culture-negative, randomly chosen stool samples from patients with suspected enteroviral disease were positive by the test. These findings demonstrate a high sensitivity and an apparently high specificity of PCR for detection of enteroviruses in stool samples. Therefore, the methodology may be useful in the laboratory diagnosis of enterovirus infections.

Base Sequence↗
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

Indomethacin modulation of monocyte cytokine release following pelvic irradiation for cancer.

Pelvic irradiation for urogenital cancer reduced monocyte release of tumour necrosis factor alpha (TNF-alpha). Addition of indomethacin to monocyte cultures increased TNF-alpha production after but not before irradiation. E. coli lipopolysaccharide (LPS) increased TNF-alpha release before as well as after radiation therapy and addition of indomethacin to LPS-stimulated monocytes further increased TNF-alpha production following radiotherapy. Spontaneous interleukin-1 (IL-1) release was increased in the cancer patients and was not significantly affected by radiation therapy. LPS increased IL-1 release before as well as after irradiation, but indomethacin did not further change IL-1 secretion. These findings suggest that prostaglandins differentially regulate TNF-alpha and IL-1 release. Administration of cyclo-oxygenase inhibitors during radiation therapy might increase TNF-alpha release in vivo and thereby enhance the host defence against tumours.

Aged↗
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↗
PubMed1991

General aspects on the diagnosis of HIV infection.

For the laboratory diagnosis of HIV infection antibody assays with unprecedented sensitivity and specificity have been developed. In combination with proper confirmatory tests, these assays enable an accurate diagnosis of HIV infection to be made in almost all cases. In special cases, most notably during very early infection, in seronegative individuals with strong suspicion of infection and in babies of infected mothers, other methods, in particular antigen detection, HIV isolation and PCR, may be utilized.

HIV↗
PubMed1990

[PCR--a highly sensitive method for identification and study of virus infections].

Viral infections can be diagnosed with using methods of molecular biology. Provided at least part of the gene sequence is known for the virus under consideration, the PCR (polymerase chain reaction) technique can be used to identify such viruses as HIV, papilloma virus, cytomegalovirus, herpes simplex virus, enterovirus, the hepatitis viruses and diarrhoeagenic viruses. Developments in this field have occurred with unprecedented rapidity. The review is primarily focused on fields where the techniques of molecular biology have crucially contributed to our knowledge of uiral pathogenesis.

Cytomegalovirus Infections↗
PubMed1990

Detection of human immunodeficiency virus-1 by polymerase chain reaction and virus cultivation.

Peripheral blood of 57 patients with antibodies to human immunodeficiency virus 1 (HIV-1) and of five HIV-1 seronegative subjects at risk for HIV-1 infection were analysed by polymerase chain reaction (PCR) and virus isolation. The virus was recovered from peripheral blood cells in 89% and from plasma in 75% of the HIV-1 seropositive cases. In contrast, proviral HIV-1 DNA was detected in all HIV-1 seropositive patients by dot blot hybridization of the amplified fragments. The intensities of the dot blot reactions were less pronounced in asymptomatic HIV-1 seropositive individuals than in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), suggesting an increase in proviral DNA with advancing disease. Three of five seronegative patients with signs or symptoms suggesting HIV-1 infection, but none of the controls, were positive for HIV-1 DNA by one or two primer pairs. These results show a high sensitivity of the PCR for detecting HIV-1 DNA in patients of all stages of HIV-1 infection. Proviral DNA can also be detected in some individuals without detectable antibodies to the virus. The virus load in peripheral blood, as determined by virus cultivation and PCR, seems to increase with progression of the infection.

Adult↗
PubMed1990

Quantitative detection of brain aberrations in human immunodeficiency virus type 1-infected individuals by magnetic resonance imaging.

The brains of 65 individuals with antibodies to human immunodeficiency virus type 1 (HIV-1), 20 HIV-1 seronegative homosexual men, and 75 heterosexual controls were examined by a quantitative magnetic resonance imaging technique. A white matter aberration was detected most frequently in patients with AIDS-related complex (ARC) or AIDS, but also in asymptomatic HIV-1 seropositive persons and in HIV-1 seronegative homosexual men, of whom two of three tested were reactive for HIV-1 DNA by polymerase chain reaction. The aberration was not found in the control group. Brain atrophy was mainly confined to patients with ARC or AIDS. The brain lesions correlated with the presence of HIV-1 in cerebrospinal fluid and with elevated levels of beta 2-microglobulin and neopterin. The most pronounced brain aberrations were in patients with AIDS-dementia complex. These findings indicate that brain aberrations may occur in persons in the early stages of HIV-1 infection, although to no greater extent than in HIV-1 seronegative homosexual men. The occurrence of pronounced brain lesions seems to be associated with the presence of an advanced immunodeficiency.

AIDS Dementia Complex↗
PubMed1990

Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV-, CMV+ individuals.

In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.

Antibodies, Viral↗
PubMed1990

Childhood bronchial asthma in a desert country.

A 3 year-study of emergency room visits (total 50,300) to the paediatric clinic of the main teaching hospital in Kuwait revealed that the rates of bronchial asthmatic attacks increased significantly from 8.8% of all visits during the 1st year to 14.9% during the 3rd year. The seasonal distribution of asthmatic attacks showed maximum rates during the winter and minimum values in the summer, giving a very close inverse correlation to temperature and direct correlation to relative humidity. A similar, excellent correlation was seen between asthmatic attacks and upper respiratory infections. Occurrence of atmospheric pollen, which characteristically shows a bi-annual pattern i Kuwait, was not found to correlate with asthma attack rates. Neither was there any demonstrable effect of dust storms on the frequency of asthmatic attacks in the children. Independent of season, the boy to girl ratio among the asthma cases was remarkably constant, around 2:1.

Asthma↗