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J Blomberg

Publications and source records attributed to J Blomberg.

At least 73 records · Page 4Linked to original sources
PubMed1990

Increased incidence of Kaposi sarcoma in Sweden before the AIDS epidemic.

Clinical factors of possible importance for the greater than two-fold rise in the incidence of Kaposi sarcoma of the elderly in Sweden before the AIDS epidemic were reviewed in 63 regional patients. 5 patients had lymphoproliferative disease before or at the time of Kaposi sarcoma, and 4 patients had been receiving steroids (including 1 with lymphoma) at diagnosis. 2 of these 9 patients plus 2 additional patients had received blood transfusions 1-9 years before diagnosis. None of 17 patients tested was positive for HIV-1, and none had signs of an unexplained progressive immune defect. Of the evaluable cases, 27% had diabetes mellitus and 7% had had previous myocardial infarction. However, only the frequency of congestive heart failure (47%) was significantly greater than that of an ambulatory control group (P = 0.001) in the age group 75-84 years. Exposure to cytomegalovirus (CMV) was not more common in 15 Kaposi sarcoma patients than in an age and sex matched control group. No single factor could account for increased Kaposi sarcoma among the elderly. If the classical form has an infectious aetiology, the tumour could arise after effective transmission of the agent (as by a transfusion), especially combined with some degree of immune deficiency or perhaps congestive failure late in life.

Adult↗
PubMed1990

Identification of regions of HIV-1 p24 reactive with sera which give "indeterminate" results in electrophoretic immunoblots with the help of long synthetic peptides.

We analyzed nine sera from persons unlikely to be HIV infected which had an IgG reactivity directed against HIV-1 p24, and in two cases also to its precursor p55, but to no other HIV proteins, nor to proteins of the H9 host cell, in electrophoretic immunoblots (EIB). These sera are also referred to as having an indeterminate HIV EIB pattern or as HIV antibody false positive sera. Seven of nine sera reacted with longer (61-77 amino acids) and none with shorter (17-25 amino acids) p24-derived peptides in enzyme immunoassays (EIAs). This is compatible with a conformational (discontinuous) nature of the epitopes involved in many false positive HIV-1 p24 antibody reactions. Four sera reacted with an N-terminal, one with an internal, and two with a C-terminal fragment. Each of the seven sera thus only reacted with one of the long p24 peptides. The specificity and singularity of the reaction was further demonstrated by competition and/or absorption experiments with synthetic peptides. In contrast, 18 of 20 confirmed HIV-1+ sera with p24 reactivity in EIB reacted with at least one and often several of the longer peptides, most frequently the C-terminal one. Thus, the distribution of peptide reactivity of true HIV-1 antibody-positive sera was different from that of the falsely reactive sera. According to two of several explanations, these antibodies may have arisen because of (1) molecular mimicry by chance or by functional selection, (2) immunization by activation, noninfectious exposure, or infection involving non-HIV endogenous or exogenous retroviral antigens. The latter gains some support from our finding of antibody reactions with capsid proteins of the simian viruses, simian sarcoma-associated virus (SSAV), and Mason-Pfizer monkey retrovirus in some of the p24 +/- p55 reactive sera.

Adult↗
PubMed1990

Differential IgG subclass responses to epitopes in transmembrane protein of HIV-1.

The human IgG subclass response to epitopes of gp41, the transmembrane protein of HIV-1, was characterized. Twenty sera that reacted with a synthetic peptide, residues 583-599 of the env product, were analyzed in subclass-specific enzyme immunoassays with this and three other peptides: the inverted sequence (599-583; HIV-env:inv), an overlapping sequence (586-606), and one derived from the 3' end of the env gene (848-863). Also, the IgG subclass reactivities with the 583-599, 586-606 and 604-625 sequences of sera from 38 patients in various stages of HIV infection were studied. IgG1 was the most prevalent subclass. Most of the few IgG2-IgG4 reactions occurred with the peptide of the strongest antigenicity, HIV-env 604-625. The sera with detectable IgG2-IgG4 reactivity were titered to allow subclass comparisons in regions below absorbance plateaus. Two sera showed proportionately higher IgG3 relative to total IgG reactivity with HIV-env 583-599 than with HIV-env 586-606, which is indirect evidence that distinct antibody populations in these sera recognize these overlapping peptide sequences. Individual differences in the antibody response to this region may affect the immunologic control of the virus. Isotype analyses can contribute to dissection of these individualities, as shown here. High IgG reactivity with HIV-env 583-599, which was linked to absence of symptoms, resided largely in the IgG1 subclass. We found no other unambiguous association between clinical status and any IgG subclass pattern.

AIDS-Related Complex↗
PubMed1990

Antibodies to a putative HIV gp41 immunosuppressive peptide, pHIVIS (583-599), do not correlate significantly with outcome in HIV infection.

We have studied the prevalence of antibodies to peptides derived from the transmembrane protein of HIV, gp41. Previous work has suggested that the presence of antibodies to the gp41 peptide known as pHIVIS (env 583-599) is associated with protection from immunosuppression in HIV infection. We studied 171 sequential sera from 55 HIV-1-infected people in various clinical stages of disease. There was no significant association between antibodies to pHIVIS and clinical status in this study. Although pHIVIS has sequence similarity to the putative immunosuppressive region of the C-type oncornaviruses (p15E), antibodies to this peptide do not appear to be associated with protection from immunosuppression in natural HIV infection.

Amino Acid Sequence↗
PubMed1990

Characterization of herpes simplex virus type 1-induced Fc receptor in its interaction with rabbit immunoglobulin G (IgG).

Herpes simplex virus (HSV) induces a receptor on infected cells that is able to bind the Fc part of immunoglobulin G (IgG). We have examined some basic physicochemical and binding properties of the Fc receptor induced on HSV-1 infected green monkey kidney (GMK) cells in its interaction with rabbit IgG. Fixation of HSV-1 infected cells with glutaraldehyde, formaldehyde, acetone or ethanol did not inhibit the Fc binding ability. The binding specificity of the receptor was not affected by ethanol treatment and all subsequent binding studies were performed with cells treated with ethanol. The receptor was detected within 4 hours of infection and the binding increased until 16 hours post infection. The interaction between ligand and receptor was dependent on pH with a binding optimum around pH 8.0 and 8.5. EDTA, but not EGTA, inhibited receptor binding, suggesting participation of divalent cations in the receptor-ligand interaction. Inhibition of binding was also seen when cells were preincubated for 30 min at 56 degrees, 60 degrees and 100 degrees C in contrast with cells incubated at 37 degrees and 45 degrees C. The number of binding sites on ethanol-treated GMK cells 18 hours after infection was estimated to be around 4 x 10(6)/cell and the affinity constant at approximately 2 x 10(7) M-1.

Animals↗
PubMed1990

The site of an immune-selected point mutation in the transmembrane protein of human immunodeficiency virus type 1 does not constitute the neutralization epitope.

We previously reported the in vitro generation of a neutralization-resistant variant of the molecularly cloned isolate of human immunodeficiency virus type 1 (HIV-1), HXB2D. The molecular basis for the resistance was shown to be a point mutation in the env gene, causing the substitution of threonine for alanine at position 582 of gp41. Here, we show the variant to be resistant to syncytium inhibition as well as to neutralization by the immune-selecting serum. Moreover, 30% of HIV-positive human sera able to neutralize the parental virus have significantly decreased ability to neutralize the variant. As the A-to-T substitution thus has general relevance to the interaction of HIV-1 with the host immune system, we investigated further the biologic and immunologic bases for the altered properties. Synthetic peptides corresponding to the 582 region failed to compete in infectivity, neutralization, or syncytium inhibition assays and did not elicit neutralizing antibodies. Furthermore, human antibodies, affinity purified on synthetic peptide resins, bound to gp41 and peptides from the 582 region but did not possess neutralizing antibody activity. Some viral constructs in which the AVERY sequence in the 582 region was altered by site-directed mutagenesis were not infectious, indicating that the primary structure in this region is crucial for viral infectivity. Constructs predicted to possess a local secondary structure similar to that of the variant nevertheless behaved like the parental virus and remained neutralization sensitive. These results suggest that the requirements for neutralization resistance in this region are very precise. Our results with synthetic peptides show that the 582 region does not by itself constitute a neutralization epitope. Moreover, the degree of flexibility in amino acid substitution which allows maintenance of neutralization sensitivity suggests that position 582 does not form part of a noncontiguous neutralization epitope. The basis for neutralization resistance of the immune-selected variant is more likely a conformational change altering a neutralization epitope at a distant site.

Amino Acid Sequence↗
PubMed1990

Cross-reactivity with SIVmac in east African HIV-1-positive sera: evidence against double infection with HIV-1 and a SIVmac/HIV-2-like virus.

IgG antibodies reactive with simian immunodeficiency virus isolated from a rhesus monkey suffering from simian acquired immunodeficiency syndrome (SIVmac, strain 239, a virus which is very closely related to human immunodeficiency virus type 2-HIV-2) were found in 18 of 120 Swedish and 8 of 11 east African confirmed HIV-1 antibody positive (HIV-1 ab+) sera, both by enzyme immunoassay and electrophoretic immunoblotting (p = 1 x 10(-6). In electrophoretic immunoblotting most of the cross-reactivity of SIVmac-reactive sera occurred on p27, the major gag protein of SIVmac. The possibility that SIVmac antibody reactivity could be due to double infection with HIV-1 and a SIVmac-related virus was eliminated by the results of absorptions between sera of Swedish and west and east African origin and viral antigens (SIVmac and North American or African/Haitian strains of HIV-1) coupled to agarose beads. HIV-2 ab+ and SIVmac reactive west African sera recognized SIVmac epitopes unrelated to HIV-1, whereas HIV-1 ab+, SIVmac reactive east African, and Swedish sera recognized SIVmac epitopes cross-reactive with epitopes present in both African and North American HIV-1 strains. No unique SIVmac-reactive African HIV-1 epitopes could thus be defined. Neither did absorption of Swedish and African HIV-1-positive sera with different HIV-1 strains (1 Haitian, 2 Zairian, and 1 North American) give evidence for unique epitopes.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Seroepidemiology of human retroviruses in Ogun State of Nigeria.

We analyzed sera collected during 1987 and 1988 from 385 healthy business employees of both sexes, of Ogun state in Nigeria, for antibodies to the 3 human retroviruses HIV-1, HIV-2 and HTLV-I. No serum was HIV-1 positive, 1 was HIV-2 positive and 2 were HTLV-I positive. A few sera were false-positive in the antibody screening tests which preceded the confirmatory antibody tests. In the confirmatory tests, we found that in the HIV-1 Western blot test 1 serum reacted only with the HIV-1 gag protein p17, and 2 sera reacted only with the HIV-1 pol proteins p64, p53 and p31. None of these reactivities fulfill internationally accepted criteria for HIV-1 seropositivity. We conclude that HIV-1 was rare in the study population and that HIV-2 and HTLV-I are present at a low frequency. The false positive serological reactions observed are similar to those described previously from Africa and elsewhere. The findings emphasize the importance of routinely testing blood donations for antibodies to these retroviruses in Nigeria.

Adolescent↗
PubMed1989

Detection of IgA antibodies against human papillomavirus in cervical secretions from patients with cervical intraepithelial neoplasia.

Although human papillomavirus (HPV) is involved in the etiology of cervical carcinoma, there are no cervical carcinoma-specific HPV serologic tests available. We investigated the presence of broadly cross-reactive IgA antibodies to papillomavirus (PV) in cervico-vaginal secretions from patients with condylomata and cervical intraepithelial neoplasia (CIN). Purified bovine PV (BPV) virions were used as antigen in an enzyme-linked immunosorbent assay (ELISA). Forty-two women whose ages ranged from 20 to 50 participated in the study. Eight of 9 patients with CIN had IgA antibodies against PV in their cervical secretions. Three of 9 patients with koilocytosis and condylomas but no CIN had IgA antibodies to PV. Six of 24 women with normal Pap-smear and colposcopy also had IgA antibodies against PV in their cervical secretions. The proportion of IgA-positive cervical secretions was significantly higher in the CIN group than in the normal group (p less than 0.005). Our data suggest that IgA antibodies to PV may be a useful marker for CIN.

Adult↗
PubMed1988

Presence of antibodies to a putatively immunosuppressive part of human immunodeficiency virus (HIV) envelope glycoprotein gp41 is strongly associated with health among HIV-positive subjects.

The IgG response to gp41 (envelope glycoprotein of Mr 41,000) of the human immunodeficiency virus (HIV) was studied with eight synthetic peptides derived from three different regions of the protein. We tested sera from 17 HIV-seronegative and 68 HIV-seropositive subjects in an enzyme immunoassay. No HIV antibody-negative serum reacted with any of the peptides. The peptide HIV-env 583-599 has a sequence similarity with immunosuppressive peptides derived from the transmembrane proteins of other retroviruses. Antibodies to this 17-mer (HIV-env 583-599; hereafter also referred to as pHIVIS, putative HIV immunosuppressive sequence) were detected in 27 of the 35 sera from healthy HIV-positive persons but only in 1 of the 33 sera from patients with HIV-related disease. Another 17-mer, displaced four amino acids N-terminally from pHIVIS, reacted with fewer of the sera from healthy seropositive subjects than pHIVIS but with no serum from ill seropositive patients. HIV-env 586-603, which shares two-thirds of its sequence with pHIVIS, reacted with the sera from nearly all subjects, regardless of clinical status. The remaining five peptides did not discriminate between healthy and ill seropositive subjects either but gave lower reactivity rates. HIV-positive sera thus exhibited distinct patterns of reactivity with subsequences of gp41. We have mapped two overlapping epitopes within a narrow part of gp41; antibodies to the most N-terminally located of the two--i.e., the pHIVIS-reactive antibodies--might counteract a possible immunosuppressive effect of gp41.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Specificities and sensitivities of three systems for determination of antibodies to human immunodeficiency virus by electrophoretic immunoblotting.

Electrophoretic immunoblotting (EIB [Western blotting]) has emerged as the major method for verification of seropositivity for human immunodeficiency virus (HIV) and therefore needs to be thoroughly characterized. The specificities of three EIB systems, our own and two commercial systems, were studied with anticellular sera and serial dilutions of human sera. We demonstrated that in one system, anti-HLA classes I and II gave bands comigrating with viral proteins, which can be controlled by EIB with uninfected H9 cells. In addition, animal antisera, including anti-immunoglobulin enzyme conjugates, occasionally reacted with HIV gag proteins, necessitating appropriate controls. Whereas none of 10 blood donors reacted at the standard dilution in serum (1/100 or 1/400) in any of the three systems, 6, 1, and 2 of 10 donors reacted with p24, p55, or both at a dilution of 1/10 for the three systems tested. Thus, nonspecific reactions can arise in several ways and justify critical EIB interpretation. The sensitivity of the three systems was studied by comparative titrations and direct quantification of bound immunoglobulin G (IgG). In the titrations with all three, the minor anti-HIV bands p53 and p64, coded from pol, were often detectable in higher dilutions than were antibodies to any other HIV protein. The minimum visible amounts of IgG bound per HIV protein band estimated by extra- and interpolation in densitometric curves and liquid scintillation counting of radiolabeled patient IgG were approximately 0.1, 0.05, and 0.02 ng per band in the three systems. One of the commercial systems had both the highest sensitivity and highest specificity.

Antibodies, Viral↗
PubMed1988

Quantification of immunoglobulin on electrophoretic immunoblot strips as a tool for human immunodeficiency virus serodiagnosis.

Electrophoretic immunoblotting (EIB [Western blotting]), the main method for verification of human immunodeficiency virus (HIV) seropositivity, needs thorough characterization and standardization. We explored the possibilities of quantifying immunoglobulin G (IgG) bound to EIB strips both by densitometry of the peroxidase-stained bands and by measurement of radioactivity with labeled anti-HIV IgG. The radioactivity method is inherently more exact but was more cumbersome. However, despite saturation phenomena at high IgG densities, the densitometric method was more convenient and yielded reproducible estimates of the amount of bound IgG. We found it useful primarily for documentation of changes in the relative abundance of antibodies to different HIV proteins from individual patients over time. To explore the potential usefulness of the method, we studied a small set of HIV-seropositive persons. The average p24/gp41 color yield ratios and standard deviations in 3 persons with recent seroconversion, 15 healthy subjects, and 6 diseased HIV-seropositive persons were 6.6 +/- 0.9, 2.3 +/- 1.9, and 1.3 +/- 0.5, respectively. These data are in accord with previous qualitative or semiquantitative observations but are too limited for any conclusions regarding the use of quantitative EIB for prognostic use with individual patients. Quantitative EIB is a valuable tool for comparative methodological studies and for research on the protective role of anti-HIV antibodies in acquired immunodeficiency syndrome pathogenesis. Its possible use in prognostication for individual patients must be evaluated in long-term studies.

Acquired Immunodeficiency Syndrome↗