Search PubMed⌕ Search

Biomedical subjects

C Nielsen

Publications and source records attributed to C Nielsen.

At least 109 records · Page 6Linked to original sources
PubMed1994

Neutralization epitopes on HIV pseudotyped with HTLV-I: conservation of carbohydrate epitopes.

One mechanism for expanding the cellular tropism of human immunodeficiency virus (HIV) in vitro is through formation of phenotypically mixed particles (pseudotypes) with human T lymphotropic virus type I (HTLV-I). In this study we found that pseudotypes allow penetration of HIV particles into CD4-negative cells, previously nonsusceptible to HIV infection. The infection of CD4-negative cells with pseudotypes could be blocked with anti-HTLV-I serum but failed to be significantly inhibited with anti-HIV serum or a V3-neutralizing anti-gp120 monoclonal antibody. This may represent a possibility for pseudotypes to escape neutralization by the immune system in vivo. Previous reports have suggested that carbohydrate structures may be conserved neutralization epitopes on retroviruses. In this study, the neutralizing capacity of lectins and anti-carbohydrate monoclonal antibodies was found to block infection by cell-free pseudotypes in CD4-negative cells. We suggest that although viral cofactors might expand the tropism of HIV in vivo, HIV and HTLV-I seem to induce common carbohydrate neutralization epitopes.

Antibodies, Monoclonal↗
PubMed1994

Connecticut physicians' knowledge and needs assessment of environmentally related health hazards--a survey.

Health care professionals for the most part, have had little or no formal education in environmental or occupational medicine. A survey tool was created to determine the educational needs of physicians in Connecticut related to environmental medicine. The questionnaire targeted four informational areas: demographics, diagnosis of environmentally caused illnesses, knowledge of environmental hazards specific to Connecticut's Superfund sites, and preference of educational materials. Results of the survey indicated that Connecticut physicians are interested in obtaining more information about environmental hazards; that there is a need for basic information about toxic waste sites, their contaminants, and the diseases associated with them; and finally, that patients are now questioning physicians about environmental hazards, especially those popularized by the media. Clearly, physicians can play a key role in educating the public about environmental hazards.

Connecticut↗
PubMed1993

Synthesis and anti-HIV activity of 5-alkoxymethyl-3'-azido-2',3- dideoxyuridines.

Methyl 3-azido-5-O-tert-butyldiphenylsilyl-2,3-dideoxy-D-erythro-furanosi de (3) was coupled with silylated 5-hydroxymethyluracil (1a) and its C1-C6 alkyl ethers 1b-g to give the corresponding protected nucleosides 4a-g which were deprotected with Bu4NF to afford 3-azido nucleosides 5a-g and 6a-g. The alpha-anomers 6f,g show moderate activity against HIV. No significant activity against HSV-1 was found for the compounds 5 and 6.

Antiviral Agents↗
PubMed1993

Pertussis immunization and characteristics related to first seizures in infants and children.

In a previous study in which we examined the relationship of pertussis immunization to the onset of neurologic disorders during 1967 and 1968 and during 1972 and 1973 in Denmark, there were 554 children with initial onset of epilepsy and 2158 children with first febrile convulsions. In the study population there were 112 children with epilepsy and 229 children with febrile convulsions for whom the exact date of pertussis immunization and the exact date of the onset of illness were known. We analyzed selected clinical variables by specific time intervals between pertussis immunization and the first seizure. In the children with epilepsy, no relationship was found between time of pertussis immunization and the specific variables that were examined. In contrast, the following characteristics in children with febrile seizures were significantly more common when pertussis immunization had occurred within 3 days, compared with more than 7 days of the event: first seizure more than 10 minutes in duration, the occurrence of more than one seizure, the longest seizure (when there was more than one) more than 10 minutes in duration, and the occurrence of a seizure described as focal. The lack of specific characteristics in epilepsy that had its onset in a temporal relationship to pertussis immunization is further evidence that pertussis vaccine does not cause this disorder. The cause of increased severity of febrile seizures apparently associated with pertussis immunization is unknown.

Humans↗
PubMed1993

Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection.

OBJECTIVE: To characterize the biological properties of HIV isolates obtained at the time of primary infection, and relate this to the subsequent course of the infection. METHODS: Syncytium-inducing (SI) capacity, tropism for cell lines (MT4 and H9) and replication rate were determined in 49 HIV isolates obtained from 17 HIV seroconverters. Thirteen of the 17 patients had a symptomatic primary HIV infection. Correlation between biological phenotype and clinical progression was analysed. RESULTS: SI isolates were recovered in six patients from the first sample taken during primary infection, non-SI (NSI) isolates only were identified in 10 of the patients and isolation culture was negative in one patient. For all patients from whom SI virus was initially isolated, this phenotype persisted during the follow-up period (range, 17-219 weeks). The duration of fever during primary infection was longer for patients with SI isolates than for patients with NSI isolates (P = 0.05). Both types of isolates were associated with a significant fall in CD4 lymphocytes during follow-up (P < 0.05). Patients with SI isolates developed HIV-related immune deficiency more rapidly than patients with NSI isolates (P < 0.05). CONCLUSIONS: The biological phenotype of HIV strains isolated during the time of seroconversion may be an important determinant of the subsequent course of the infection.

CD4-Positive T-Lymphocytes↗
PubMed1993

Neutralizing antibody response during human immunodeficiency virus type 1 infection: type and group specificity and viral escape.

The paradox that group-specific neutralizing antibodies (NA) exist in the majority of human immunodeficiency virus type 1 (HIV-1)-infected patients, whereas the NA response against autologous HIV-1 virus isolates is highly type-specific, motivated us to study the type- and group-specific NA responses generated upon presentation of escape virus, and the viral epitopes involved in the escape. Patients with demonstrable escape virus all developed group-specific NA, which were detectable after a delay and disappeared prior to disease development. The sera tested inhibited the binding of recombinant soluble gp120IIIB to cell-associated CD4, but group-specific virus neutralization required binding of NA to HIV-1 prior to viral attachment to target cells. Consecutive escape virus isolates were tested for sensitivity to neutralization by heterologous sera. Only minor differences were demonstrated, suggesting that the majority of the change in neutralization sensitivity is driven by the selective pressure of type-specific NA. Furthermore, no differences were observed in sensitivity to neutralization by anti-carbohydrate neutralizing monoclonal antibodies or the lectin concanavalin A, indicating a conserved nature of certain carbohydrate neutralization epitopes during escape. Finally the V3 sequence of three sets of consecutive virus isolates were analysed revealing amino acid mutations in V3 sequences of all escape virus isolates. The biological significance of these variations was confirmed further by the demonstration of changes in sensitivity to neutralization by anti-V3 monoclonal antibodies. These results strongly suggest a participation of the NA response against the V3 loop in the immunoselection of escape virus.

Amino Acid Sequence↗
PubMed1993

An ultrastructural study of HIV-infected human dendritic cells and monocytes/macrophages.

The ultrastructure of dendritic cells (DC) isolated from HIV-negative blood donors revealed three morphologically distinct cell types: type I had an irregularly shaped nucleus with a high content of heterochromatin and numerous short pseudopodia; type II possessed a smoother boundary, a "blast-like" nucleus and a few veil-like protrusions; and type III resembled veil-like cells (DC) in the lymph. HIV induced a productive virus infection in type II DC with budding of virus solely from the cell surface. HIV was observed in cytoplasmic vacuoles of type III DC, but no budding of virus was observed from these cells. HIV was not observed in type I DC. Isolated monocytes were cultured for 8-15 days in order for these cells to differentiate into macrophages. Cultured monocytes and macrophages became highly vacuolized when infected with HIV strains and productive virus infection was localized in intracytoplasmic vacuoles. Budding from the cell surface was rarely observed. When monocytes were co-cultured with CD4(+)-infected lymphocytes, specialized electron-dense contact zones were observed in monocyte-like cells. Virus particles were found outside some of these contact zones, indicating that the zones may play a role in the penetration and transfer of virus from cell to cell.

Antigens, CD↗
PubMed1993

Continuous blood gas monitoring in haemodialysis using an electrode inserted in the extracorporeal dialysis circulation.

The aim of this study was to evaluate the usefulness of continuous gas monitoring during haemodialysis using an oxygen- and carbon dioxide-sensitive electrode inserted in the 'arterial' line from the arteriovenous fistula. We investigated 15 patients with chronic renal failure, treated with regular bicarbonate haemodialysis. The PO2 and PCO2 were measured by the new method and compared to conventional blood gas analysis of the 'arterial' blood from the dialysis circulation. We found the in situ gas sensors were stable and there was no systematic difference between gas tensions measured by in situ and conventional blood gas measurements. The standard deviations of the difference between paired measurements for PO2 and PCO2 were 1.3 and 0.4 kPa, respectively. Therefore, the method can be used to detect major changes in blood gas tensions during haemodialysis.

Adult↗
PubMed1993

Evaluation of the combination effect of different antiviral compounds against HIV in vitro.

3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2',3'-didehydrothymidine stavodine; TIBO: tetrahydro-imidazole-benzodiazepin) had a synergistic effect at all concentrations, agents that disturb the infectivity of virus (CAS: Castanospermine; AME: Amphotericin B Methyl Ester) exerted a strong synergistic effect at low concentrations, and finally compounds interfering with the adhesion/penetration process of virus (ConA: Concanavalin A; DS: dextran sulfate) were most potent with AZT when used in rather high concentrations. At this moment in the HIV epidemic, these observations suggest that combinations of antiviral compounds should be evaluated in clinical trials, with the major emphasis on nucleoside analogues and compounds influencing the infectivity of the virus.

Antiviral Agents↗
PubMed1993

Enhancement of retroviral infection in vitro by anti-Le(y) IgG: reversal by humanization of monoclonal mouse antibody.

Monoclonal mouse IgG3 antibody (ABL 364) against the carbohydrate Le(y) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when propagated in both transformed and normal lymphocytes. Enhancement was independent of complement, occurred with both lymphocytes and monocytes as target cells, and did not use either L(ey) epitopes on target cells for cross-linkage of virus to the cell or the Fc part of the antibody as a ligand for any cellular receptor. For enhancement to occur, binding of anti-Le(y) antibody to virus was required to take place before virus binding to its specific receptor with no indication of any alternative pathway of infection, as evidenced by abrogation of enhancement by anti-CD4 MAb or soluble recombinant CD4, and also the inability of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HTLV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of ABL 364 also enhanced infection, a human/mouse chimeric antibody and a fully humanized antibody had no enhancing effect on free virus infection. We suggest that binding of anti-Le(y) ABL 364 or its F(ab)2 fragment induced a conformational change in the gp120 oligomers facilitating the process of infection, and that this function was abrogated by the IgG1 Fc of the chimeric and the humanized antibodies. The observations indicate that the non-paratope domains of antiviral antibodies can influence their function as neutralizing or enhancing for infection.

Animals↗
PubMed1993

Calcium acetate versus calcium carbonate as phosphorus binders in patients on chronic haemodialysis: a controlled study.

The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis. Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study. It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l (0.34 mg/dl) (P = 0.021, 95% confidence limits 0.02-0.21 mmol/l; 0.06-0.65 mg/dl) during calcium acetate treatment. The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased.

Acetates↗
PubMed1992

Synthesis of 3'-alkylthio-2',3'-dideoxy nucleosides with potential anti-HIV activity from 2-deoxy-D-ribose, using a phosphorus pentoxide reagent.

Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1.

Antiviral Agents↗
PubMed1992

Development of resistance to zidovudine in HIV strains isolated from CD4+ lymphocytes and plasma during therapy.

An assay based on production of HIV antigen in cultures of CD4+ lymphocytes infected 'in vitro' with cell-free virus was established. Using this assay it was possible to isolate, propagate and reliably determine the zidovudine susceptibility of HIV isolates from all patients despite differences in cellular tropism and syncytium inducing capacity. Using this assay, differences in zidovudine susceptibility of 52 serial isolates obtained from 16 patients before and after initiation of therapy were examined. HIV with a 10- to 100-fold reduced susceptibility to zidovudine were isolated from 13 patients as early as 4 months after initiation of therapy. Number of months of zidovudine treatment was strongly associated with development of viral resistance, and high CD4 cell counts tended to be associated with lower rates of development of resistance. That patients can harbor mixtures of virus strains with different susceptibility to zidovudine was confirmed by the differences in susceptibility between isolates obtained simultaneously from CD4+ lymphocyte and plasma, and by the differences in susceptibility between virus strains isolated from clones of CD4+ lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Sensitive non-radioactive detection of HIV-1: use of nested primers for the amplification of HIV DNA.

This report describes the use of the polymerase chain reaction (PCR) for the non-radioactive detection of HIV-1 proviral genomic sequences in HIV-1 infected cells. We have developed a sensitive assay, using three different sets of nested primers and our results show that this method is superior to standard PCR for the detection of HIV-1 DNA. The assay described features the use of a simple and inexpensive sample preparation technique and a non-radioactive hybridization procedure for confirmation of results. To test the suitability of the assay for clinical purposes, we tested cell samples from 76 anti-HIV-1 positive patients. All were positive for at least one primer set: 88% were positive for all three sets of primers; 9% were positive for two sets of primers and 3% were positive for only one set of primers. It provides a useful approach to the study of HIV-1 infection in patient samples where genomic copies often are present at such low numbers that they are otherwise undetectable.

Base Sequence↗
PubMed1992

N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study.

Sixty-five patients with chronic bronchitis were studied at five different centres in a double-blind, randomized trial. Two parallel groups were treated with either N-acetylcysteine or placebo by metered dose inhalers for 16 weeks. Following a 1-week run-in period, each patient recorded subjective impressions of the drug action on their bronchitic symptoms in a diary once a week. In addition, exacerbations were registered. Lung function testing and adverse effects were evaluated by four visits to the chest clinics during the 16 weeks. We could not demonstrate that N-acetylcysteine by metered dose inhalers had any significant effect on patients' feeling of well-being, sensation of dyspnoea, intensity of coughing, mucus production, or expectoration or lung function. Its effect in reducing exacerbations could not be estimated because of a very low number of exacerbations reported. N-acetylcysteine inhalation was safe when used over a 16-week period.

Acetylcysteine↗
PubMed1992

FK 383 DS, a new silica gel for the determination of unsaturated haptocorrin and transcobalamin II in serum.

The ability of selective absorption of the polypeptide transcobalamin II by silica gel was used for the determination of the unsaturated cobalamin binding capacity of haptocorrin and transcobalamin II. Two different silica gels, QUSO G 761 and FK 383 DS, were compared by Sephacryl gel-filtration and by determination of unsaturated haptocorrin and transcobalamin II from forty different patient sera. It was found that the silica gels act identically for this purpose.

Chromatography, Gel↗