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J O Nielsen

Publications and source records attributed to J O Nielsen.

At least 19 recordsLinked to original sources
PubMed2001

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts.

Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P <.001) and reduced thymic output in infants of HIV-positive mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P <.001). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function.

Anti-HIV Agents↗
PubMed2000

Prevalence and prognostic significance of infection with TT virus in patients infected with human immunodeficiency virus.

No clear association between human disease and TT virus (TTV) has been documented. A possible pathogenic role of TTV was investigated in patients infected with human immunodeficiency virus (HIV). TTV serum concentrations were estimated in 185 HIV-infected patients by dilution polymerase chain reaction. Of these, 149 (76%) were TTV-positive, compared with 18 (7%) of 252 Danish blood donors (P<. 001). Of the HIV-infected patients who were TTV-positive, 72 (51%) had high TTV viremia (>/=5 times the highest concentration observed among blood donors, i.e., >/=3.5x105 TTV/mL of serum). High TTV viremia was associated with decreased survival (P<.001; relative hazard [RH], 2.0). There was a correlation between lower CD4+ T cell counts and higher TTV titers (P<.01). In a Cox regression model, CD4+ T cell count (P<.001), age (P<.001), HIV viral load (P<.001), beta2 microglobulin (P<.02), and high TTV viremia (P<.01; RH, 1.9) were independent predictors of survival. TTV is suspected to be an opportunistic pathogen with an independent influence on HIV progression.

AIDS-Related Opportunistic Infections↗
PubMed2000

Sumatriptan increases the proliferation of peripheral blood mononuclear cells from HIV-infected individuals and healthy blood donors in vitro.

HIV infection is characterized by the loss of CD4+ T cells as well as the loss of T-cell function, leading to severe immunodeficiency. The proliferative capacity of T cells measured in vitro as responses to antigens and mitogens is severely reduced during HIV infection. An increased level of the intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to cause impaired proliferative capacity of peripheral blood mononuclear cells (PBMC) from HIV-infected individuals in vitro. Sumatriptan, a 5HT1d receptor agonist, inhibits the activity of adenylyl cyclases, the enzymes responsible for regulation of the intracellular levels of cAMP. In a preliminary study sumatriptan increased the proliferative responses of PBMC to a polyclonal activator in vitro in 9 of 10 HIV-seropositive individuals (p=0.007), and in 7 of 9 healthy blood donors (p=0.05). This was probably due to a decrease in the intracellular level of cyclic AMP.

Adult↗
PubMed2000

The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals.

This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was given three times weekly for 12 weeks to 30 HIV-infected patients that had been treated with HAART for at least 24 weeks and not yet achieved CD4 counts above 350 CD4+ cells/microl. Blood samples were collected at weeks 0, 2, 4, 8, and 12, and again 12 weeks after termination of the G-CSF treatment. Significant increase in absolute numbers of circulating CD34+ cells was detected in the treatment group (P = 0.006). The function of progenitor cells was examined in vitro using a colony-forming unit (CFU) assay, and increase in the number of CFU/ml was detected (P = 0.005). In order to estimate the effect of G-CSF on in vivo function of progenitors the white-blood count was determined. Significant increase in white-blood count was found (P < 0.001), while hemoglobin and platelet count decreased (P = 0.001 and P = 0.013, respectively). Significant increase in the CD4 count occurred, but correlation between the numbers of progenitors and the CD4 count was not found. These data suggest that G-CSF mainly increases the number and differentiation of myeloid progenitors.

Anti-HIV Agents↗
PubMed2000

Decrease in immune activation in HIV-infected patients treated with highly active antiretroviral therapy correlates with the function of hematopoietic progenitor cells and the number of naive CD4+ cells.

This study was conducted to determine the impact of immune activation, cytokine production and apoptosis on the naive CD4+ cell count and the function of hematopoietic progenitor cells during the initial phase of highly active antiretroviral therapy (HAART). Blood samples from 11 HIV-infected patients were collected prior to HAART and after 4 and 12 weeks of therapy. Flow cytometry was used to determine the naive CD4+ count and activated T cells. The cloning efficiency of progenitor cells was determined using a colony-forming cells assay. Finally, apoptosis and cytokine production were determined. During the study period, the naive CD4+ count and the cloning efficiency increased significantly. Immune activation was found in HIV-infected patients and decreased during HAART. The level of immune activation correlated negatively with both the naive CD4+ count and the function of progenitor cells. A negative correlation was found between apoptosis and the naive CD4+ count. Alterations in cytokine production during HAART or correlation between cytokine production and the naive CD4+ count or the cloning efficiency of progenitor cells were not detected. In conclusion, immune activation in HIV-infected patients treated with HAART is inversely correlated with the function of progenitor cells and the naive CD4+ count.

Anti-HIV Agents↗
PubMed1999

Quantification of intracellular metabolic fluxes from fractional enrichment and 13C-13C coupling constraints on the isotopomer distribution in labeled biomass components.

A method for the quantification of intracellular metabolic flux distributions from steady-state mass balance constraints and from the constraints posed by the measured 13C labeling state of biomass components is presented. Two-dimensional NMR spectroscopy is used to analyze the labeling state of cell protein hydrolysate and cell wall components. No separation of the biomass hydrolysate is required to measure the degree of 13C-13C coupling and the fractional 13C enrichment in various carbon atom positions. A mixture of [1-13C]glucose and uniformly labeled [13C6]glucose is applied to make fractional 13C enrichment data and measurements of the degree of 13C-13C coupling informative with respect to the intracellular flux distribution. Simulation models that calculate the complete isotopomer distribution in biomass components on the basis of isotopomer mapping matrices are used for the estimation of intracellular fluxes by least-squares minimization. The statistical quality of the estimated intracellular flux distributions is assessed by Monte Carlo methods. Principal component analysis is performed on the outcome of the Monte Carlo procedure to identify groups of fluxes that contribute major parts to the total variance in the multiple flux estimations. The methods described are applied to a steady-state culture of a glucoamylase-producing recombinant Aspergillus niger strain.

Aspergillus niger↗
PubMed1999

Improvement of lymphocyte proliferation in human immunodeficiency virus infection after recombinant interleukin-2 treatment.

In this study, the effect of recombinant interleukin-2 (rIL-2) on the function of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients was examined. Using polymerase chain reaction (PCR), an impaired ability of PBMC from 8 patients to respond upon mitogen stimulation with expression of IL-2 and IL-2 receptor (IL-2R) messenger ribonucleic acid (mRNA) was found compared with healthy donors (p = 0.02 and p = 0.05, respectively). Flow cytometry was used to determine the expression of p55 interleukin-2 alpha-receptor (CD25) after phytohaemagglutinin (PHA)-stimulation. Induced CD25 expression in response to stimulation was lower in patient cells than in donor cells (in CD4+ (p = 0.01) and in CD8+ (p = 0.03)). After rlL-2 treatment, the functionality of ex vivo expanded PBMC from patients was restored to the level found in donors. Finally, the induced gene expressions for IL-2 and IL-2R were positively correlated (p < 0.0001), suggesting that the activation of the IL-2 and IL-2R genes in humans may share a common activation pathway, as has been found in monkeys infected by simian immunodeficiency virus (SIV). These results indicate the existence of a reversible IL-2 and IL-2R defect at the pretranscriptional or transcriptional level in PBMC from patients. This may help explain the T-cell anergy found during HIV-infection.

Adult↗
PubMed1999

Treatment with granulocyte colony-stimulating factor decreases the capacity of hematopoietic progenitor cells for generation of lymphocytes in human immunodeficiency virus-infected persons.

An obstacle to stem cell gene therapy for AIDS is the limited numbers of hematopoietic progenitors available. Granulocyte colony-stimulating factor (G-CSF) is used for mobilization of progenitors, but little is known about the functional characteristics of mobilized progenitors, and immature and T cell progenitors may not be mobilized. This study examined the effect of G-CSF on the function of progenitors. Ten human immunodeficiency virus-infected patients received G-CSF (filgrastim, 300 microgram/day) for 5 days. Absolute numbers of immature and T cell progenitors did not increase. The ability of CD34+ progenitor cells to generate lymphocytes was examined by use of thymic organ cultures. The mean number of lymphocytes generated per CD34+ cell on day 0 was 0.72 and on day 4 was 0.09 (P<.003). The number of CD4+ cells generated per CD34+ cell was significantly reduced after G-CSF treatment. Thus, G-CSF increased the number of mature progenitor cells but did not increase T cell progenitors.

Animals↗
PubMed1998

Chemokine receptor polymorphism and autologous neutralizing antibody response in long-term HIV-1 infection.

We have previously reported that slowly progressing HIV infection (SPI) was associated with the presence of contemporaneous autologous neutralizing antibodies. In contrast, a group of individuals with more rapidly progressing infection (RPI) generally lacked these antibodies. To understand the importance of autologous neutralizing antibodies in SPI more fully, we have now conducted a prospective study taking consecutive blood samples from the individuals with SPI (8 patients) and RPI (10 patients). Blood sampling in the group with SPI was done 110 and 123 months after the estimated seroconversion and at similar time points in the group with RPI. Virus isolation was attempted at both time points in both groups of individuals; crossed neutralization assays were set up with autologous virus. These confirmed our previous finding of significant autologous neutralizing titers in the group with SPI (geometric mean titer [GMT] 8.7 versus 1.6 in SPI and RPI, respectively; p = 0.0048). However, not all individuals with SPI possessed autologous neutralizing antibodies, indicating that other factors may be decisive for SPI. Furthermore, neutralizing antibody titers did not increase from early to late serum samples. Finally, late virus isolates from individuals with SPI generally remained sensitive to neutralization by early serum samples. Virus phenotype (SI/NSI) and CCR5 genotype was determined for all individuals. Neither showed significant correlation with SPI. However, all SPI individuals who were heterozygous for the CCR5 deletion were infected with virus of NSI phenotype. In contrast, all RPI individuals who were heterozygous for the CCR5 deletion were infected with virus of SI phenotype (p = .028). Thus, a beneficial effect of having a partly nonfunctional CCR5 coreceptor may depend on the viral SI/NSI phenotype.

CD4 Lymphocyte Count↗
PubMed1998

[Hepatitis B vaccination status among Danish physicians].

As part of a nation-wide questionnaire survey among Danish doctors, the incidence of hepatitis B vaccination was studied. For each specialty the findings were related to the risk of hepatitis B exposure assessed by the incidence of percutaneous and mucocutaneous blood exposure (PCE and MCE). A total of 6256 of 9375 doctors (67%) responded and 6005 (64%) questionnaires were eligible for analysis. Only 34.3% of the doctors had been vaccinated against hepatitis B, ranging from 8.9% in Psychiatry to 56.9% in Obstetrics-Gynaecology. The annual incidence of PCE and MCE was high in surgical as well as non-surgical specialties with an average of 3.0 PCE and 3.9 MCE per person. In conclusion all doctors must be considered at risk of exposure to hepatitis B during part of or the entire career. The current level of hepatitis B vaccination is insufficient. Hepatitis B vaccination of all doctors before entering clinical work seems to be indicated.

Blood-Borne Pathogens↗
PubMed1998

[On locomotives].

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Bibliometrics↗
PubMed1998

[Percutaneous blood exposure among Danish physicians. Mechanisms and prevention].

The study describes the mechanisms of percutaneous blood exposure (PCE) among Danish doctors and discusses rational strategies for prevention. Data were obtained as part of a nation-wide survey of occupational blood exposure. The most recent percutaneous or mucocutaneous exposure within the previous three months was described. Of 9375 doctors, 6005 (64%) participated. A total of 971 PCE were described. Inattentiveness contributed to 30.5%. Use of fingers rather than instruments was a contributing cause of 36.9% of 483 PCE on suture needles. Common concomitant causes in such cases (n = 199) were poor space in (30.2%) or view of (18.6%) the operation field. Of 689 PCE in surgical specialties, 17.4% were inflicted by colleagues. Up to 53.3% of PCE on hollow-bore needles could be attributed to unsafe routines only. In conclusion, education in safer working routines are needed in all specialties. Introduction of safer devices should have a high priority in surgical specialties, and should be considered in non-surgical specialties too.

Accidents, Occupational↗
PubMed1998

[Poor compliance with universal precautions among Danish physicians].

In a nation-wide survey among Danish doctors, the compliance and reasons for non-compliance with universal precautions (UP) and the associated circumstances of mucocutaneous blood exposure (MCE) were studied. Of 9384 questionnaires, 6256 (67%) were returned and 6005 were eligible for analysis. Only 35% complied with the basic principles of UP. Compliance with protective barrier use in surgical versus non-surgical specialties was: Gloves 63.0% and 23.4%, masks 55.2% and 17.6% and protective eyewear 11.5% and 4.0% respectively. Common given reasons for non-compliance were: "Interferes with working skills", "forget", "wear spectacles", "not available", "too much trouble to get" or "gloves do not fit". Of 741 MCE described in detail, an estimated 84-98% were potentially preventable if appropriate barriers had been worn. More than half of MCE were preventable by two interventions only: Compulsory use of protective eyewear during operations and of gloves during insertion of peripheral i.v.-catheters. In conclusion compliance with UP is unacceptably low and the majority of MCE were potentially preventable if appropriate barriers had been worn.

Accidents, Occupational↗