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Biomedical subjects

A Sönnerborg

Publications and source records attributed to A Sönnerborg.

At least 145 records · Page 8Linked to original sources

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↗

Fine analysis of intrathecally synthesized anti-HIV IgG1-4 by peptide mapping.

ELISAs utilizing HIV-derived synthetic peptides as antigen were used to analyze serum and CSF IgG1-4 from 15 HIV infected patients. Intrathecally synthesized IgG1-4 reactive to one or several HIV-derived peptides were detectable in 12 of 15 patients. Intrathecally synthesized anti-peptide IgG was more common in patients with neurological symptoms than in those without. CSF reactivity not paralleled by serum reactivity was detected to HIV-peptides in 4 patients. IgG1-4 to gp41 was relatively more frequent in the CNS than IgG1-4 to gag. Intrathecal IgG synthesis to the gp120 peptide was not detected in any patient. The anti-peptide responses were dominated by IgG1. Intrathecal IgG2 and 4 synthesis was found in 2 and 5 patients, respectively. IgG3 synthesis intrathecally was not detected in any of the patients. ELISAs detecting IgG1-4 to HIV-derived synthetic peptides are feasible to analyze the fine specificities of intrathecal IgG. The mapping of idiotypes and isotypes of IgG synthesized in the CNS will increase the possibilities of elucidating B-cell regulation in the CNS and which viral components evoke immune responses.

Gene Products, gag↗

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↗

Differences in PCR reactivity between HIV proviruses from individuals in Ethiopia and Sweden.

The polymerase chain reaction (PCR), using primer pairs in the gag, pol, and env regions, was used in a comparative study of HIV-1 DNA in peripheral mononuclear blood cells from HIV-1-seropositive individuals in Ethiopia and Sweden. Although all Swedish samples were positive by PCR, the reactivity was more pronounced in samples from late stages than in those from early stages of infection. Six of nine Ethiopian samples from HIV-1-seropositive patients were positive by PCR, but the reactions were much weaker than those observed for Swedish samples, and in most cases seen with one primer pair only. These results suggest that the burden of HIV-1 DNA in peripheral mononuclear blood cells increases with advancing disease. PCR using primer pairs designed to detect HIV-1 infection in Europe and North America is not always suitable for the detection of HIV-1 infection in Ethiopia. The differences in PCR reactivity could possibly be a consequence of differences regarding host responses to the virus in the two countries, but more likely due to genomic differences between HIV-1 strains prevalent in Ethiopia and Sweden.

AIDS-Related Complex↗

[A magnetic tomography study: 3 out of 4 HIV-I infected men suffer subcortical pathologic changes].

Forty HIV-1-sero-positive and 15 HIV-1 antibody negative homosexual or bisexual men were examined by means of magnetic resonance imaging (MRI) and 20 neuropsychological tests. Subcortical, mainly frontal cerebral pathological aberrations were detected in 75 per cent of the patients on examination with ultra low field MRI computer assisted classification. No such changes were found among controls. The extent of the subcortical aberrations detected correlated with severity of immune deficiency, stage of infection (CDC classification), duration of infection, and reported neuropsychological symptoms. Neuropsychological testing showed impairment in memory function, concentration capacity, and fine motor control in the patients but not in the controls.

Acquired Immunodeficiency Syndrome↗

Relationship between the occurrence of virus in plasma and cerebrospinal fluid of HIV-1 infected individuals.

Attempts to isolate human immunodeficiency virus type 1 (HIV-1) were carried out on cerebrospinal fluid (CSF) and blood plasma samples from 111 HIV-1 infected subjects in various stages of infection. HIV-1 was recovered at a low rate from CSF of persons with normal immunological parameters but frequently from patients with abnormal values, in all stages of immune system involvement. Isolation from plasma was positive in the majority of the patients, in all stages of infection, with a frequency that was related to the degree of immunodeficiency. HIV-1 could be recovered from the CSF of most patients (74%) with viremia when 85 paired specimens of 58 patients were analyzed. By contrast, HIV-1 was isolated from CSF, but not from plasma, in one case only. HIV-1 p24 antigen measured by an enzyme-linked immunosorbent assay (ELISA) was detectable in only four CSF samples compared with 15 serum samples in paired specimens. These findings indicate that most patients with HIV-1 infection have circulating cell-free infectious virus in the blood and simultaneously demonstrable HIV-1 in the CSF. Replication of HIV-1 exclusively in the central nervous system (CNS) appears to be a rare event.

Acquired Immunodeficiency Syndrome↗

Detection of antibodies against myelin basic protein and increased levels of HIV-IgG antibodies and HIV antigen after solubilization of immune complexes in sera and CSF of HIV infected patients.

Fifteen HIV seropositive patients were studied. It was possible to enhance detection of HIV antigen and HIV and myelin basic protein (MBP) antibodies after dissociation of immune complexes by acid hydrolysis. HIV p24 antigen was then detected in four patients, three of whom were previously antigen negative. In 14 patients the treatment resulted in increased anti-HIV IgG subclass levels. Anti-MBP IgG was detected in 12 patients. Intrathecal synthesis of anti-MBP IgG subclasses was found in eight patients, five of whom had symptoms from the central nervous system.

Acquired Immunodeficiency Syndrome↗

Detection of cell-free human immunodeficiency virus in cerebrospinal fluid by using immune scanning electron microscopy.

The cerebrospinal fluid of 52 patients with human immunodeficiency virus type 1 (HIV-1) infection was incubated with polystyrene microspheres coated with monoclonal antibodies specific for HIV-1 core or envelope antigens. The beads were then collected on a filter surface and inspected by scanning electron microscopy (SEM). In 37 of 51 samples from subjects with chronic HIV-1 infection and from all three patients with primary HIV-1 infection, with or without neurologic symptoms, particles of 50-75 nm and 100-125 nm were visualized on beads coated with antibodies to HIV-1 core and envelope antigens, respectively. No such binding of particles was detected in the controls. Findings using immune SEM, which was found to be as sensitive as virus isolation, indicate that HIV-1 can replicate in the central nervous system (CNS) of patients with primary or chronic HIV-1 infection without causing neurologic symptoms. Production of cell-free virus seems to occur in the CNS of the majority of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗

Antigen detection in primary HIV infection.

Serial blood samples were obtained from 21 homosexuals who had developed symptomatic primary infection with human immunodeficiency virus (HIV) after a median incubation time of 14 days. During the first two weeks after the onset of illness HIV antigen (p24) was detected in the blood by enzyme linked immunosorbent assay (ELISA). During the second and third weeks after the onset of illness p24 antibody was detected by Western blot assay and antigen concentrations rapidly decreased to undetectable values. Dissociation of antigen-antibody complexes showed complexed antigen during the phase of declining concentrations of free antigen. Neither free nor complexed antigen was detected in any serum samples for several months thereafter, which suggested that failure to detect HIV antigen reflected low or absent synthesis of viral protein rather than masking of antigen by antibodies. Reappearance of HIV antigen with a fall in p24 antibody concentration was observed in a few patients six months or more after the onset of disease. The combined use of antigen and antibody assays made it possible to obtain evidence of infection with HIV in all of the 95 serum samples tested, illustrating the usefulness of these assays for diagnosing infection with HIV in its early stages.

Acquired Immunodeficiency Syndrome↗

IgG subclass reactivity against human immunodeficiency virus (HIV) and cytomegalovirus in cerebrospinal fluid and serum from HIV-infected patients.

Cerebrospinal fluid (CSF) and serum samples from 17 patients seropositive for the human immunodeficiency virus (HIV) were analysed for specific IgG1-4 against HIV and cytomegalovirus (CMV). Measles IgG was studied as a reference to detect blood-brain barrier (BBB) defects. All patients had IgG1 antibodies against HIV in both CSF and serum, and all had CMV IgG1 in serum (16 in CSF). Anti-HIV IgG was synthesised intrathecally in 11 patients, IgG3 in three patients, and IgG4 in three patients. Intrathecal production of anti-CMV IgG1 was found in three patients, IgG2 in one, IgG3 in three, and IgG4 in one. Intrathecal anti-HIV IgG synthesis could be demonstrated in all stages of the disease. Analysis of all IgG subclasses allowed intrathecal HIV and/or IgG production to be detected also in patients in whom intrathecally synthesised IgG was restricted to IgG2, 3, or 4. The expression of HIV-specific IgG subclasses in CSF and serum was more restricted in AIDS patients than in HIV-infected persons without clinical AIDS. On the contrary, the largest number of CMV-specific IgG subclasses was found in AIDS patients. Intrathecal HIV or CMV IgG subclass production was seen both with and without neurological symptoms. The peripheral T4 cell counts were not obviously related to neurological symptoms. Even patients with low peripheral T4 cell counts had evidence of intrathecal antibody synthesis against HIV and sometimes CMV, suggesting a retained helper function of T cells in the central nervous system.

AIDS-Related Complex↗

Efficient isolation of HIV from plasma during different stages of HIV infection.

Attempts to isolate human immunodeficiency virus (HIV) from blood plasma using inoculation of pellets from ultracentrifuged samples into cultures of peripheral blood mononuclear cells (PBMC) resulted in a high overall recovery rate (75%) of the virus from 76 patients in various stages of HIV infection. The recovery rate was dependent on the stage of infection; in patients with acquired immunodeficiency syndrome (AIDS) it was 100%, in AIDS-related complex (ARC) 86%, in persistent generalized lymphadenopathy (PGL) 64%, and in asymptomatic patients 54%. The HIV isolation rates compared favorably with those obtained after cocultivation of patient and target PBMC (overall recovery rate 67%). HIV was isolated from plasma but not from PBMC in 8 cases, whereas the reverse was true in 3 of 71 simultaneously tested cases. Isolation from plasma was found to be superior to detection of serum p24 antigen for the demonstration of HIV (positivity rates 75% and 30%, respectively). The time to appearance of p24 antigen in cultures inoculated with HIV-containing plasma samples was inversely related to the presence of detectable p24 antigen in serum. There was a significantly shorter time to culture positivity of plasma samples from AIDS and ARC patients than from PGL and asymptomatic patients. These results suggested that there is a progressive increase in the concentrations of infectious HIV in plasma from the asymptomatic to the AIDS stage. HIV isolation from plasma samples is a reliable means of demonstrating HIV viremia and has obvious advantages over the more commonly used cocultivation procedures. The frequent occurrence of cell-free, infectious HIV in plasma suggests that the majority of HIV-infected patients have a relative lack of functional neutralizing antibodies against the virus, at least during the late stages of disease.

AIDS-Related Complex↗

Human immunodeficiency virus infection of the brain. II. Detection of intrathecally synthesized antibodies by enzyme linked immunosorbent assay and imprint immunofixation.

Sera and CSF from 29 patients in early and late stages of HIV infection were analysed for intrathecal antibody production. Elevated CSF-IgG indices indicating intrathecal IgG synthesis were demonstrated in 9 patients while 4 of 18 patients tested had oligoclonal IgG bands in the CSF. Analysis of HIV-specific antibodies by enzyme-linked immunosorbent assay (whole antigen and site-directed ELISA) and calculation of "antibody indices" (CSF/serum antibody quotient divided by CSF/serum albumin quotient) indicated intrathecal HIV antibody synthesis in 19 patients. Analysis of serum and CSF antibodies by an imprint immunofixation (IIF) method showed intrathecal synthesis of predominantly polyclonal HIV-IgG antibodies in 11 of 13 patients examined. IIF analysis of antibodies to six other infectious agents showed no intrathecal antibody production except in one patient who had minor fractions of intrathecally synthesized IgG antibodies to varicella zoster virus. The present results demonstrate that an intrathecal HIV-specific antibody response may be present in both early and late stages of HIV infection, and indicates that HIV may reach the brain at an early stage of infection.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus infection of the brain. I. Virus isolation and detection of HIV specific antibodies in the cerebrospinal fluid of patients with varying clinical conditions.

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 29 subjects with varying severity of HIV infection. Virus could be isolated from patients in all stages of disease including patients with primary HIV infection and asymptomatic carriers. In the early stages of infection free virus was infrequently present in the CSF but could be isolated from the cells present in CSF. This suggests that HIV may reach the brain at a very early stage of infection and that initially there is little production of virus from infected cells. In the late stages of HIV infection, associated with increasing severity of immunodeficiency, free virus could readily be isolated from the CSF. With one exception, all of these patients had neurological and/or psychiatric symptoms, as compared to only 2 (of 13) subjects in the early stages of infection. All patients with HIV-specific antibodies in serum had antibodies also in CSF. Examined by a radioimmunoprecipitation assay, CSF was more often found to contain antibodies to the precursor (p55) of viral core proteins than the corresponding serum of the patients. We propose that immune disturbances have an essential pathogenic role in the neurological/psychiatric symptoms associated with HIV infection, possibly through allowing increased viral expression in the central nervous system.

AIDS-Related Complex↗

Isolation frequency of human immunodeficiency virus from cerebrospinal fluid and blood of patients with varying severity of HIV infection.

Isolation of the human immunodeficiency virus (HIV) has been attempted from the cerebrospinal fluid (CSF) of 63 subjects at different stages of HIV infection, including asymptomatic carriers and patients with or without neurologic or psychiatric complications. In addition blood was collected from 40 of these subjects for virus isolation. HIV could be isolated from the CSF at all clinical stages with an overall frequency of 40%. In contrast, the frequency of HIV isolation from the blood was lower (32%) at the early stages of infection than in patients with severe disease (77%). HIV isolation from the CSF was more frequently positive in patients with neurologic or psychiatric complications than in patients showing no such disturbances (48 and 32%, respectively).

Acquired Immunodeficiency Syndrome↗

Detection of immunoglobulin M antibody in primary human immunodeficiency virus infection.

Consecutive serum samples obtained from 20 homosexual men during symptomatic primary HIV infection were examined by a variety of IgG and IgM antibody assays. All sera obtained 2-5 weeks after onset of disease contained IgM anti-HIV as demonstrated by an IgM antibody capture assay. The IgM antibodies appeared during the 2 first weeks of illness, reached peak titres at 2-5 weeks and declined thereafter to undetectable levels at 2-3 months after the onset of disease. By contrast, IgG anti-HIV appeared later, during the second week after the onset of symptoms, and did not reach maximal levels until the IgM response had waned. The first IgM antibodies to appear were directed against gag proteins. IgM antibodies against env antigens were found less frequently and later in the course of the disease. These results suggest that IgM antibody determination may be helpful in the diagnosis of early HIV infection as a possible addition to the combined use of antigen detection and a second generation ELISA, which, in the present study, was found to be highly reliable for diagnostic purposes.

Acquired Immunodeficiency Syndrome↗