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Biomedical subjects

G Biberfeld

Publications and source records attributed to G Biberfeld.

At least 145 records · Page 8Linked to original sources

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immunodeficiency virus (SIVsm).

Five healthy cynomolgus monkeys were inoculated intravenously with simian immunodeficiency virus (SIVsm) propagated in human lymphocytes. All five animals became infected. Virus was recovered from blood mononuclear cells and viral antigen was detected in serum 12 days postinoculation (PI) in all inoculated animals. Virus was also isolated in all five animals tested 74 to 226 days PI. Antibodies to different structural proteins of SIV and HIV-2 were demonstrated by ELISA, Western blot, and radioimmunoprecipitation assay from day 31 PI concomitantly with a reduction of viral proteins in the serum. Reappearance of antigen accompanied by a fall in antibody to gag products (p26) was observed in two monkeys 69 days PI. All SIV-infected monkeys showed a pronounced decrease in CD4+ lymphocytes demonstrable already 12 days PI. They also developed persistent lymphadenopathy. Thus, infection of cynomolgus monkeys with SIVsm mimics events in human immunodeficiency virus infection in humans but the course of evolution of pathogenic events in the monkey is markedly compressed. This experimental model will be useful for evaluation of HIV vaccines and antiviral testing.

Acquired Immunodeficiency Syndrome↗

HIV-2-associated AIDS and HIV-2 seroprevalence in Bissau, Guinea-Bissau.

During a 6-month period in 1987, we examined patients clinically suspected of the acquired immune deficiency syndrome (AIDS) at the national hospital in Bissau, the capital of Guinea-Bissau, and found 20 cases that fulfilled the criteria for AIDS. The two most prevalent major symptoms were weight loss and diarrhea, and the most common minor symptoms generalized lymphadenopathy and generalized dermatitis. Six of 20 patients died within a couple of months. Nineteen of 20 patients were tested for human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) antibodies and were shown to be HIV-2 seropositive. During the same time period, a seroprevalence study of HIV-2 and HIV-1 was carried out, including 2,122 patients or healthy persons in Bissau. Antibodies to HIV-2 were demonstrated by enzyme-linked immunosorbent assay and verified by Western blot analysis in 8.6% (46/535) of prenatal women, in 7.9% (9/114) of women attending a family-planning clinic, in 4.4% (19/427) of applicants for scholarships, in 17.6% (16/91) of blood donors tested during the first 2 months and 5.3% (10/189) of blood donors tested during the following months, in 5.7% (2/35) of police officers, in 36.7% (11/30) of female prostitutes, in 15.8% (97/614) of outpatients suspected of having tuberculosis, and in 55.2% (48/87) of patients clinically suspected of AIDS or AIDS-related disease. One of 2,001 subjects tested had antibodies specific for HIV-1. Another subject had an antibody pattern compatible with both HIV-1 and HIV-2 infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Lack of cross-reaction in antibody-dependent cellular cytotoxicity between human immunodeficiency virus (HIV) and HIV-related West African strains.

Sera from individuals infected with human immunodeficiency virus (HIV) and HIV-related West African viruses can mediate high-titered, virus-specific antibody-dependent cellular cytotoxicity (ADCC) in all stages of infection. No cross-reactive ADCC can be detected between HIV and HIV-related West African strains LAV-2, HTLV-IV, and SBL-6669. Because these two groups of viruses have antigenically distinct envelope glycoproteins, ADCC-mediating antibodies are most likely directed against envelope antigens. For HIV-specific ADCC, this was further confirmed by using sera reacting with HIV envelope but negative for antibodies against viral core antigens.

Africa, Western↗

Prognostic significance of immunoglobulin isotype expression in B-cell non-Hodgkin's lymphoma.

Lymph node biopsies from 170 patients with untreated non-Hodgkin's lymphomas (NHL) of B-cell type were immunophenotyped and analyzed for the Ig heavy and light chain isotypes and their relation to prognosis. IgM alone was more frequently seen in high grade (53%) compared to low grade (20%) NHL. In contrast, IgM/IgD isotypes were more frequent in low grade (47%) than in high grade NHL (20%). IgG or IgA heavy chain, alone or in combination with other heavy chain isotypes, were expressed with the same frequencies in both low (32%) and high (27%) grade NHL. Clonally restricted kappa light chain expression was noted in 64% of low grade and 66% of high grade NHL patients. Only in chronic lymphocytic leukemia (CLL) and immunocytoma (IC) was a shorter survival time noted for patients with tumors expressing IgG and/or IgA heavy chains compared to those expressing IgM or IgM/IgD (P less than 0.001). This difference was not seen as being low grade follicle center cell-derived (FCC) or high grade NHL. The expression of kappa light chains on the tumor cells was associated with a significantly longer survival in CLL and IC patients only (P less than 0.01).

Adult↗

Evaluation of commercial enzyme immunoassays for anti-HIV-1 using East African sera.

Sera from 622 blood donors collected in 1986 and 1987 in Tanzania were screened for antibodies to HIV-1 by seven different commercial enzyme-linked immunosorbent assay (ELISA) kits. All ELISA-positive sera were tested by Western blot analysis and many of them also by radioimmunoprecipitation assay (RIPA). Sixty-seven sera were confirmed positive. Eight sera, which were repeatedly positive on only one or two of the ELISA kits and showed weak, doubtful reactions on Western blot and RIPA, were considered indeterminate and were not included in the calculations of sensitivity and specificity of the various ELISA kits. The sensitivity of the ELISAs was as follows: Organon Vironostika: low cut-off 74.6%; Organon Vironostika: high cut-off 62.7%; Du Pont: 85.1%; Pasteur: 78.7%; Abbott: 80.8%; Abbott recombinant: 94.0%; Wellcozyme: 82.1%; Wellcozyme monoclonal: 98.5%. The specificity was as follows: Organon Vironostika: low and high cut-off 100%; Du Pont: 94.7%; Pasteur: 99.3%; Abbott: 100%; Abbott recombinant 98.7%; Wellcozyme: 99.8%; Wellcozyme monoclonal: 98.5%. In conclusion, the two new generation kits tested, Wellcozyme monoclonal and Abbott recombinant, had the highest sensitivity whereas the sensitivity of the first-generation tests was unexpectedly low.

AIDS Serodiagnosis↗

HIV-serology and lymphocyte subsets in relation to therapy and clinical development in haemophiliacs.

389 Swedish patients with haemophilia A, B or von Willebrand's disease were examined for HIV-1 antibodies. T-cell subsets were measured in 260 of them. HIV-1 antibodies were found in 98 of these patients. Of the 199 patients with severe or moderate haemophilia A, 44% were seropositive. They had seroconverted between 1979 and 1983. HIV-1-seropositive patients had significantly decreased numbers of CD4 cells and increased numbers of CD8 cells. The seronegative haemophilia A patients had significantly increased numbers of CD8 cells. The T-cell subsets were followed for a median of 40 months in 73 seropositive patients. All groups of patients, at different clinical stages, showed decreasing numbers of CD4 cells. The most pronounced decrease was seen in the patients who developed AIDS, followed by the group which developed HIV-related signs or symptoms. HIV antigen in serum and antibody pattern in Western blot and ELISA were followed in 89 patients. HIV-1 antigen was present and p24 antibodies were lacking in 11% and 13% of asymptomatic subjects, in 13% and 20% of patients with persistent generalized lymphadenopathy, in 33% and 38% of patients with other HIV-related signs or symptoms and in 5/6 of the AIDS patients, respectively. In conclusion, the decrease of CD4 cells and the presence of HIV antigen and/or absence of p24 antibodies were found to be prognostic markers for HIV disease.

Acquired Immunodeficiency Syndrome↗

Prevalence of HIV-1 and HIV-2/HTLV-IV infections in Luanda and Cabinda, Angola.

A seroepidemiological study of human immune deficiency virus type 1 (HIV-1) and HIV-2/human T-lymphotropic virus type IV (HIV-2/HTLV-IV) infections was performed in Angola in October 1986. Until then five cases of acquired immune deficiency syndrome (AIDS) had been registered in Angola. During this study, another three cases with clinical AIDS were found and confirmed by HIV-1 serology. A total of 1,215 sera from groups of healthy persons and patients were tested for HIV-1 and HIV-2/HTLV-IV antibodies by enzyme-linked immunosorbent assays (ELISA). Sera positive by ELISA were also tested by Western blot (WB) analysis. In Luanda, the capital, HIV-1 antibodies were demonstrated in 0.4% (2/452) of male blood donors, in 0.3% (1/357) of pregnant women, in 1% (1/100) of tuberculosis patients, in 4% (4/94) of patients at medical wards, and in none of 22 women hospitalized with pelvic infections. In the Cabinda province, 11% (4/38) of postnatal women at a maternity ward were found to be HIV-1 seropositive, but only 2% (1/55) of other hospitalized patients and none of 32 male blood donors or 59 healthy persons in a village on the border to Zaire. Specific antibodies to HIV-2/HTLV-IV were not found in any of the sera. However, 16 out of 17 HIV-1 positive sera cross-reacted with HIV-2/HTLV-IV core proteins by WB. In October 1987, 280 of the blood donors from Luanda were retested for HIV-1 antibodies and one of them was found to have seroconverted during the previous year.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Enzyme immunoassays for the demonstration of antibodies to HIV-2SBL-6669 and HTLV-IV (SIVmac).

Enzyme-linked immunosorbent assays (ELISA) were developed for the demonstration of antibodies to HIV-2 using disrupted virions of the SBL-6669 isolate of HIV-2 and the so-called human T-lymphotropic virus type IV (HTLV-IV), recently found to be identical with the simian immunodeficiency virus (SIVmac), as antigens. Three hundred sera from West African subjects, attending an outward clinic in Bissau for examination of suspected tuberculosis, were tested by these two assays as well as by a commercially available anti-HIV-2 ELISA (ELAVIA II). Fifty of these sera were positive in all three ELISAs as well as in Western blot tests against HTLV-IV. Thirty-eight of these positive sera were also tested by an anti-HIV-2 Western blot kit (LAV-Blot II) with positive results. The ELISAs based on SBL-6669 and HTLV-IV antigens had a specificity of 99.6% (one false positive among 250 negative sera) whereas the specificity of ELAVIA II was 94.6% using the recommended cut-off value and 98.4% using a higher cut-off value. Another 58 sera from West African patients, clinically suspected of having AIDS or HIV-related disease, were tested for HIV-2/HTLV-IV antibodies by Western blot and by ELISA against SBL-6669 and HTLV-IV antigens; all of the 30 sera which were positive by Western blot were found to be positive in both ELISAs.(ABSTRACT TRUNCATED AT 250 WORDS)

Africa, Eastern↗

Lymphadenopathy in HIV (HTLV-III/LAV) infected subjects: the role of virus and follicular dendritic cells.

Studies of human immunodeficiency virus (HIV) associated lymphadenopathy by histopathology and immunopathology showed conspicuous changes of follicular B-cell areas from a marked hyperplasia to complete involution. Immunohistochemistry showed a corresponding increase in follicular dendritic reticulum cells (FDRC) followed by progressive destruction of these cells during involution, concomitant with invasion of follicles by T-cells. HIV gag antigens were predominantly associated with FDRC in hyperplastic follicles and diminished during involution. Virus replication was by in situ hybridization seen predominantly in follicles, presumably reflecting productive infection of CD4+ cells and/or FDRC. It is concluded that local effects of the virus play an important role in HIV lymphadenopathy. The marked cytopathogenic effects on FDRC indicate that HIV infection with lymphadenopathy represents not only a disease of CD4+ cells but also of follicular antigen presenting cells (FDRC).

AIDS-Related Complex↗

Neutralizing antibodies in relation to antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus type I.

The presence of neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) was investigated in sera from 73 HIV-1 seropositive subjects at different clinical stages. Virus neutralization was measured as survival of MT-4 cells in a 6-7 day microassay. Sixty-three sera were also tested for antibodies inducing virus-specific antibody-dependent cellular cytotoxicity (ADCC). Neutralizing antibodies were found in 59% of sera tested, the positivity rate being 50% (9/17) in asymptomatic subjects, 67% (12/18) in patients with persistent generalized lymphadenopathy (PGL) and 54% (14/26) in AIDS patients (not significant differences). ADCC antibodies were present in 43% of the sera. Neutralizing antibodies and ADCC-inducing antibodies were found simultaneously in 35% (22/63) of the sera. Neutralizing antibodies alone were found in 22% (14/63) and ADCC antibodies alone in 6% (4/63) of the sera tested. Thirty-seven per cent (23/63) of the sera were negative for both types of antibodies, 62% of the sera with neutralizing antibodies also had ADCC inducing antibodies and 85% of the sera with ADCC antibodies had neutralizing antibodies. The titres of ADCC antibodies were higher than those of neutralizing antibodies. Thus, the presence of ADCC antibodies was related to the presence of neutralizing antibodies, but no correlation was found between the titres of these antibodies in sera positive for both activities.

AIDS-Related Complex↗

Detection of antibodies which mediate human immunodeficiency virus-specific cellular cytotoxicity (ADCC) in vitro.

A method to detect antibodies which mediate antibody-dependent cellular cytotoxicity (ADCC) against HIV-infected target cells was developed. Normal lymphocytes were used as effector cells and different HIV-infected cell lines as target cells. The level of ADCC varied depending on both the effector cell function and the target cell susceptibility. For evaluation of HIV-specific ADCC, the effector function was simultaneously tested against a standard antigen (beta 2 microglobulin), expressed both on infected and uninfected target cells. The HIV-infected monocytoid cell line U937, clone 2, was found to be the most useful target cell in the present system. The detection of antibodies which induce HIV-specific ADCC killing will permit clinical and experimental analysis of the possible importance of such antibodies in protection against HIV-associated disease symptoms.

Acquired Immunodeficiency Syndrome↗

Antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus. Presence at different clinical stages.

The presence of antibodies mediating antibody-dependent cellular cytotoxicity (ADCC) against human immunodeficiency virus (HIV)-infected target cells was investigated with 170 sera from patients with varying severity of HIV infection. Approximately 40% of sera from individuals representing all stages of infection were ADCC-positive when tested against HTLV-IIIB infected 0937 clone 2 target cells. The positive sera had higher HIV antibody titers as measured by enzyme-linked immunosorbent assay compared with ADCC-negative sera. ADCC titers were lower in patients with acquired immune deficiency syndrome than in asymptomatic carriers. This decline in ADCC titer was not correlated with a general decrease of HIV antibodies. No correlation between the CD4:CD8 lymphocyte ratio and ADCC activity was found. The possible beneficial effect of ADCC-inducing antibodies early in infection is discussed in relation to the effect of ADCC-inducing antibodies in other retrovirus systems and to the nature of lentivirus infections.

AIDS-Related Complex↗

Site-directed ELISA with synthetic peptides representing the HIV transmembrane glycoprotein.

Two partially overlapping 19 and 22 amino acids long peptides representing a highly immunogenic site of the transmembranous glycoprotein (gp41) of human immunodeficiency virus (HIV) were used as antigen in ELISA tests. The results of antibody determination with this assay were compared with those of three or more conventional ELISAs and Western blot (WB) tests and radioimmunoprecipitation assay. Twenty-six sera from patients with AIDS or LAS and from asymptomatic carriers of HIV infection all showed a pronounced reaction in the peptide ELISA as well as positive results with other tests. In contrast, 27 sera from laboratory workers and blood donors were negative by all tests. A group of 39 blood donor sera, which had shown false positive or ambiguous results in the ELISAs and sometimes in WB tests employed for confirmation, also were negative in all cases with the peptide ELISA. Consecutive samples collected from individuals with primary HIV infection were also analyzed. In 6 out of 9 cases, the peptide ELISA revealed an antibody response within one month after onset of clinical symptoms and sensitivity for antibody detection equaled that of other ELISA tests. Eight sera from five West African persons infected with HIV-related viruses did not react in the peptide ELISA, reflecting differences in properties of the envelope components. The peptide ELISA used in this study appears to represent a simple technique employing chemically synthesized antigen for accurate and sensitive estimation of antibodies to the HIV group of nontransforming human retroviruses.

AIDS-Related Complex↗

Genetic analysis of a new subgroup of human and simian T-lymphotropic retroviruses: HTLV-IV, LAV-2, SBL-6669, and STLV-IIIAGM.

A new primate retrovirus, STLV-IIIAGM, has been recently isolated from healthy African green monkeys and is apparently nonpathogenic in its natural host. However, spontaneous infection as well as inoculation of STLV-IIIAGM into macaques induces a disease with clinical features that resemble human AIDS. Independent isolates of human retroviruses, serologically closely related to STLV-IIIAGM, have been obtained from healthy individuals (HTLV-IV) and patients with immunodeficiency (LAV-2FG and SBL 6669) from West Africa. The latter have also been referred to as HIV-2 because, like HTLV-III/HIV-1, they may be associated with immune deficiency, or as West African human retroviruses because of their prevalence and probable origin from that region. We have molecularly cloned the STLV-IIIAGM genome and have generated probes from the gag-pol and envelope genes to analyze the genetic relatedness of these simian and human retroviruses. Our results indicate that all these retroviruses are genetically closely related to each other, HTLV-IV and STLV-IIIAGM differing only by a few restriction enzyme sites while LAV-2FG and SBL 6669 exhibit greater polymorphism from HTLV-IV/STLV-IIIAGM. These data mirror the variable degree of relatedness among members of the first subgroup of human retroviruses, HTLV-III/HIV.

Animals↗

Radioimmunoprecipitation and Western blotting with sera of human immunodeficiency virus infected patients: a comparative study.

The sensitivity and specificity of radioimmunoprecipitation assay (RIPA) and Western blot (WB) test were compared by use of a collection of 183 sera, representing different categories of individuals, noninfected or infected with the human immunodeficiency virus (HIV). The sera were subdivided on the basis of their reactivity in at least two anti-HIV enzyme-linked immunosorbent assays (ELISA); 53 sera were negative and 61 sera were positive in both tests, whereas 69 sera showed ambiguous reactions. The reaction patterns in RIPA could be divided into 6 different groups. The same grouping could to some extent be applied to the results of WB test. RIPA provided the most efficient means for identification of the large viral envelope glycoproteins, gp120/160, whereas gp41 was detected more effectively by WB. Internal virus components reacted to a varying extent with specific antibodies in the two tests. The reaction with pol products was more pronounced with the WB tests in which extracellular material was used as antigen. In a few WB tests, however, the reaction with internal components did not reflect a prior HIV infection. No such ambiguity was observed with RIPA, reflecting the advantage of a test that uses a minimally denaturated antigen and provides appropriate conditions for identification of the large viral glycoproteins. The practical choice of confirmatory tests to be used in diagnostic laboratories requires evaluation of both the sensitivity and specificity of the tests but also their economy and convenience.

Acquired Immunodeficiency Syndrome↗