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Biomedical subjects

L R Mathiesen

Publications and source records attributed to L R Mathiesen.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of anti-carbohydrate antibodies on HIV infection in a monocytic cell line (U937).

Monoclonal antibodies (mAbs) against carbohydrate epitopes of gp120 have recently been found to inhibit HIV infection of lymphocytes in vitro thereby opening new possibilities for vaccine considerations. Antibody-dependent enhancement of infection has however come increasingly into focus. This study therefore investigated the neutralization of HIV in a monocytic cell line (U937) using mAbs against these carbohydrate gp120-epitopes. While antibodies against one of the epitopes (AI) neutralized infection of U937 cells despite binding to the Fc-receptor, one mAb against the sialosyl-Tn epitope enhanced infection. This enhancement was independent of complement and could be blocked by mAb Leu3a against the CD4-receptor. The study indicated that enhancement of infection in monocytic cells can occur by the same anti-carbohydrate antibodies that neutralize infection in lymphocytes, and that antibody mediated enhancement may depend on location of the epitope on gp120 rather than whether the antibody binds Fc-receptors.

Antibodies, Monoclonal↗
PubMed1991

Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors.

Three virus isolates HTLV-IIIB/lyA, HTLV-IIIB/lyB and HTLV-IIIB/lyO, obtained by passaging and propagating the HTLV-IIIB/H9 isolate in three separate cultures of mixed peripheral blood mononuclear cells (PBMC) from donors of blood type A, B or O, respectively, were tested for susceptibility for virus neutralization by the monoclonal antibody (MAb) AH16 directed against the blood group A epitope. MAb AH16 was previously shown to inhibit cell-free virus infection using HTLV-IIIB propagated in H9 cells. AH16 showed a concentration-dependent inhibition of the HTLV-IIIB/lyA isolate but did not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can be a target for MAb-mediated virus neutralization.

ABO Blood-Group System↗
PubMed1991

Detection of human immunodeficiency virus DNA in cultured human glial cells by means of the polymerase chain reaction.

This report describes the use of the polymerase chain reaction (PCR) for the detection of viral genomic sequences in latently infected cells. Infection with human immunodeficiency virus in cultures of human glial cells was demonstrated, using nucleic acid amplification followed by dot blot hybridization. It was not possible to detect any viral antigen production in the cultures, and attempts to recover virus by highly sensitive coculture techniques were unsuccessful, indicating that the infection was latent. The PCR technique provides a simple approach to the study of viral infection in cases where viral replication is absent, or where genomic copies are present at such low numbers that they are otherwise undetectable.

Brain Neoplasms↗
PubMed1991

Involvement of lymphocyte function-associated antigen-1 (LFA-1) in HIV infection: inhibition by monoclonal antibody.

Monoclonal antibodies (MAbs) against the alpha- and beta-chain of lymphocyte-associated antigen-1 (LFA-1) were examined for inhibition of HIV-1 infection in vitro. Infection of the T cell line MT4 and the monocytic cell line U937 by isolates HTLVIIIB and SSI-002, respectively was inhibited in a concentration dependent manner by MAb against the beta-chain but not against the alpha-chain. No cross-reactivity was found between MAb against LFA-1 and against the CD4 receptor (MAb Leu3a). MAbs against the beta-chain and the CD4 receptor were found to act synergistically in inhibiting HIV infection. These data indicate that the beta-chain of LFA-1 in addition to the CD4 receptor may be involved in HIV infection in vitro.

Antibodies, Monoclonal↗
PubMed1991

Low yield of screening for cryptococcal antigen by latex agglutination assay on serum and cerebrospinal fluid from Danish patients with AIDS or ARC.

From July 1, 1989 to September 5, 1990, 530 serum specimens and 50 cerebrospinal fluid (CSF) specimens from 334 HIV-1 infected patients, most of whom had AIDS or ARC, were analysed in a cryptococcal antigen latex agglutination assay, and all were negative. Three cases of meningitis due to Cryptococcus neoformans diagnosed by microscopy and culture in 3 HIV-1 infected patients are presented. Stored specimens of serum and CSF from these patients were assayed for cryptococcal antigen, and in all 3 the onset of meningitis was preceded by the presence of cryptococcal antigen in serum. It is concluded that the low occurrence of cryptococcosis in our patient population does not justify a routine serum screening for cryptococcal antigen.

AIDS-Related Complex↗
PubMed1990

[HIV infected women in Copenhagen. Risk factors and sex behavior].

A total of 115 women were found to be HIV-antibody positive during the period January 1985 to September 1988 in the three large hospitals in Copenhagen. Thirty-five women (31%) had been infected heterosexually, 63 (55%) were intravenous drug addicts, 12 (10%) had been infected by transfusion and in five (4%) the mode of transmission was unknown. In 1988, 73% of the women who were found to be HIV-positive were infected heterosexually while only 14% were infected in this manner in 1985. Out of the heterosexually HIV-infected women, 25 (71%) had probably been infected by a man from a risk group while nine further women were infected by a known HIV-positive man with-out connection to any risk group. Eleven women (31%) stated that they practised "safe sex" prior to the HIV test while 22 (74%) did so after the positive HIV-test, which represents a considerable improvement. Out of the drug addicted women, six (10%) stated that they had always practiced "safe sex" prior to the test while 13 (28%) did so after the HIV-test. Approximately 1/3 of these women periodically shared syringes and needles with others. It is concluded that heterosexual contact among HIV-infected women in Copenhagen is a route of transmission of significance. Women infected heterosexually appear to alter their sexual behavior when they are made aware of the positive HIV-test.

Denmark↗
PubMed1990

Derivatives of amphotericin inhibit infection with human immunodeficiency virus in vitro by different modes of action.

Three water-soluble derivatives of amphotericin B were tested for inhibition of HIV infection in vitro. The compounds amphotericin B methyl ester (AME) and N-(N'-(2-(4'-methylmorpholinio)ethyl)N"-cyclohexyl guanyl) amphotericin B methyl ester (MCG) inhibited HIV infection by 50% at 1 microgram/ml; N-(N'-(3-dimethylaminopropyl)N"-ethyl guanyl) amphotericin B (DAPEG) did so at 5-11 micrograms/ml. While the virus-inhibitory effect of AME was due to an interaction with target lymphocytes, the effect of MCG was due to a direct anti-viral action. AME increased the potential of infected cells to fuse with uninfected cells, but MCG had no significant effect on cell fusion. All compounds had a lower cellular toxicity than amphotericin B and were not toxic at concentrations below 20 micrograms/ml.

Amphotericin B↗
PubMed1990

Heterosexually acquired human immunodeficiency virus infection in women in Copenhagen: sexual behavior and other risk factors.

In order to describe the risk pattern including sexual behaviour among HIV-infected women in Copenhagen we studied the charts of all women tested seropositive between January 1985 and August 1988 in the three main hospitals handling HIV/AIDS. One hundred and fifteen women were positive for HIV antibodies: 35 (31%) were infected by heterosexual contact and 63 (55%) were intravenous drug users. Among the heterosexually transmitted cases 25 (71%) had intercourse with a man from a high risk group and nine women had intercourse with a known HIV antibody positive man without known risk factors. Use of condoms was claimed by 31% of the heterosexually-transmitted women before the HIV test, and by 74% (P = 0.002) after the test. In 1988 73% of the women tested HIV positive were infected by heterosexual contact, in 1985 only 14%. We conclude that among HIV infected women in Copenhagen heterosexual transmission is a problem. These women seem to change sexual behaviour when informed about HIV positivity.

Contraceptive Devices, Male↗
PubMed1990

Fluconazole for ketoconazole-resistant oropharyngeal candidiasis in HIV-1 infected patients.

The efficacy of fluconazole in doses ranging from 50 to 200 mg/day in controlling oropharyngeal candidiasis was retrospectively evaluated in 16 consecutive HIV-1-infected patients. 13 patients received fluconazole due to failure of treatment with ketoconazole, and among these 11 (84%) initially showed complete or partial remission of oropharyngeal candidiasis. 3 (27%) of these subsequently developed failure of treatment within a median observation period of 38 days. No major toxicities were observed. Fluconazole appears promising in the therapy of ketoconazole-resistant candidiasis.

Adult↗
PubMed1990

Early appearance of antibodies to hepatitis C virus in community acquired acute non-A, non-B hepatitis is associated with progression to chronic liver disease. The Copenhagen Hepatitis Acuta Programme.

24 consecutive patients (14 females; median age 36, range 18-77) with liver biopsy proven acute non-A, non-B hepatitis (NANBH) were assayed for antibodies to hepatitis C virus (HCV). 14 (58%) were positive initially or during follow-up. Three patients were positive within 4 weeks following onset of symptoms and 7 patients in a serum sample obtained 4-8 weeks after clinical onset. Seroconversion was documented in 7/8 patients in paired sera from the acute phase of the disease. Anti-HCV was detected in 6% and 13% of control patients with acute hepatitis A and toxic hepatitis. NANBH in 6/14 patients (43%) with anti-HCV progressed to chronic liver disease (CLD). In contrast none of the anti-HCV negative patients developed CLD (p = 0.02). In addition, 2 anti-HCV positive patients developed fulminant and fatal hepatitis. The predominant route of HCV transmission was intravenous drug abuse. It is concluded that hepatitis may be ascribed to HCV infection in more than half of patients with community aquired NANBH, that seroconversion occurs in the majority within 8 weeks following onset of symptoms and that seropositive individuals often progress to CLD.

Adolescent↗
PubMed1989

Isolation of HIV using T-lymphocyte 'panning': methodological aspects.

A technique for isolation of HIV using selective cultures of T4 cells obtained from peripheral blood by immunochemical separation was developed and optimized. Using this method infectious virus could be isolated in single isolation attempts from 89% of 35 HIV-infected patients in different stages of immunodeficiency. This isolation frequency was virtually independent of the stage of the disease, in contrast to the results obtained by the conventional isolation technique based on peripheral mononuclear cells (PMC). It is concluded that isolation of HIV from selected T4 cells is superior to other methods when isolation is attempted from healthy HIV-infected individuals.

Antibodies, Monoclonal↗
PubMed1989

Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins.

The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated complex type glycan and a triantennary bisected complex type glycan. Only lectins which bound at least one of the four types of glycans were capable of inhibiting fusion of HIV-infected cells with CD4 cells by a carbohydrate-specific interaction with the HIV-infected cells. Thus, several different glycan structures may be implicated in CD4-gp120 binding.

CD4 Antigens↗
PubMed1989

HIV neutralizing antibodies: development and association with HIV related disease.

Serum neutralization was measured in 72 sera collected during a 5.5-year period from 10 HIV infected individuals. Neutralizing antibodies (NA) were present in all sera. NA titers ranging from greater than 40 to greater than 640 were detected in sera from 4 patients, who all remained healthy and further an increase with time of NA was observed in these 4 patients. Progression to disease was observed in 3 persons with NA titers less than or equal to 40 who also lacked or lost anti-gag antibodies. Two of these patients were HIV antigenaemic prior to development of disease, whereas antigen was not detected in the remaining 7 healthy persons. A weak positive correlation (R(S) = +0.643, p less than 0.001) was found between titers of NA and whole virus antibody (WVA), with the ratios between titers (NA titer/WVA titer) varying a 100-fold. The results suggest that the presence of NA in some cases might be related to a healthy carrier state and that a combination of low titer NA with decline of anti-gag antibodies and/or HIV antigenaemia is associated with progression to clinical disease.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Disseminated histoplasmosis in a Danish patient with AIDS.

We present the first case of disseminated histoplasmosis in an AIDS patient in Europe, a 33-year-old Danish homosexual man, and recommend a detailed travel history in HIV-positive patients presenting with fever, weight loss and organomegaly. In Scandinavia disseminated histoplasmosis is rare but should be kept in mind as the disease is a major opportunistic infection in patients with AIDS. Treatment with amphotericin B followed by fluconazole was effective.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Zidovudine treatment of AIDS and ARC in Denmark 1987.

In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received treatment with zidovudine, a total observation period of 572 treatment months. 15 AIDS and 1 ARC patient died after a median of 70 days (range 2-295). In the ARC group 4 patients developed AIDS (3 Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS patients 38 new opportunistic infections were reported. 24 of these opportunistic infections occurred within 6 weeks after treatment initiation. 79 patients were observed for more than 3 months, 25 of these had their daily dose zidovudine reduced, usually from 1,200 mg to 600 mg, 9 others were temporarily off drug. HIV antigen was analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54 initially HIV antigen-positive became antigen-negative, 7 (18%) of 39 initially HIV antigen-negative became antigen-positive within the first 8 weeks of zidovudine treatment. In 57 patients the total count of CD4+ cells were evaluated. A significant increase in the number of CD4+ cells was observed during treatment. In nearly all patients an increase in MCV and a decrease in neutrophil count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions and 19 (14%) patients required multiple transfusions. The mortality among the AIDS patients was significantly lower compared to historical controls. In our experience zidovudine treatment is reasonably well tolerated and the side effects are manageable.

AIDS-Related Complex↗
PubMed1989

The value of lymph node histology in human immunodeficiency virus related persistent generalized lymphadenopathy.

Histological changes in lymph nodes were evaluated in a prospective study of 124 homosexual men who presented with generalized lymphadenopathy. The histological changes were classified according to a classification system with three stages. HIV antibodies were present in 88% of the patients. The finding of one of the three histopathological stages was highly indicative--although not absolutely pathognomonic--for HIV infection. The subsequent course of HIV infection after biopsy was significantly correlated to the histopathological changes, but it was not possible to evaluate if the biopsy added new information to that already available. Among the group of HIV infected, immediate clinical consequences of lymph node biopsy were not observed (95% confidence limits 0-3.3%). In a retrospective investigation of 123 consecutive AIDS patients, it was found that lymph node histopathology had been able to identify secondary infections and neoplasms among 10%. It is concluded that lymph node biopsy is indicated in the HIV infected patients with unexplained generalized symptoms or with atypical enlargement of the lymph nodes. The prognostic significance of lymph node histology compared to other prognostic parameters of HIV infection, remains to be determined.

AIDS-Related Complex↗