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Biomedical subjects

H W Snoeck

Publications and source records attributed to H W Snoeck.

26 records · Page 2Linked to original sources

Effects of interleukin-4 on myelopoiesis: localization of the action of IL-4 in the CD34+HLA-DR++ subset and distinction between direct and indirect effects of IL-4.

We compared the myelopoietic effects of interleukin-4 (IL-4) on CD34+HLA-DR+ and on CD34+HLA-DR++ bone marrow progenitor cells stimulated by either granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3). IL-4 stimulates G-CSF-induced colony-forming unit-granulocyte (CFU-G) and inhibits all colony types induced by GM-CSF and IL-3 in the HLA-DR++ population, but not in the HLA-DR+ population. In CD34+HLA-DR+ cells, however, a stimulation of G-CSF-supported CFU-G was also seen with sequential application of IL-4 in liquid cultures followed by G-CSF in agar cultures. In order to confirm that these are direct effects of IL-4, single-cell culture experiments were performed with CD34+HLA-DR++ cells. In these cultures IL-4 stimulates G-CSF-induced CFU-G and only inhibits colony-forming unit-macrophage (CFU-M) regardless of the CSF used to generate them.

Antigens, CD↗

Differential regulation of the expression of CD38 and human leukocyte antigen-DR on CD34+ hematopoietic progenitor cells by interleukin-4 and interferon-gamma.

We studied the effects of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) on the expression of CD38 and human leukocyte antigen (HLA)-DR on purified CD34+ bone marrow progenitor cells. CD34+CD38- and CD34+HLA-DR- cells are largely nonoverlapping populations. After culture for 4 days in IFN-gamma, the expression of CD38 and HLA-DR is significantly increased and the disappearance of the CD38- and HLA-DR- populations is virtually complete. Moreover, IFN-gamma induces a population of CD34+ cells with a very high expression of CD38 (CD34+CD38++ cells), which were absent in the initial CD34+ population. IL-4 has no effect on the expression of CD38, but induces a limited but significant increase in the expression of HLA-Dr. After culture in IFN-gamma, CD34+ cells show a higher cloning efficiency of the colony-forming unit-macrophage (CFU-M) and burst-forming unit-erythroid (BFU-E) compared to cells cultured in medium alone. After culture in IL-4, a limited increase in CFU-granulocyte (CFU-G) and BFU-E is seen, whereas CFU-G, CFU-M, and BFU-E are increased after culture in IL-4 plus IFN-gamma. We further investigated the functional properties of the CD34+CD38++ cells generated in the presence of IFN-gamma. This cell population is highly enriched for BFU-E but partially depleted of CFU-M. Most of the CFU-M were found in the CD34+CD38+/-(CD34+CD38- and CD34+CD38+ cells) population.

ADP-ribosyl Cyclase↗

Aberrant Ki-67 expression in normal bone marrow revealed by multiparameter flow cytometric analysis.

Ki-67 is a commercially available monoclonal antibody that reacts with a nuclear antigen detectable in proliferating cells only. Since its first description, it has been widely used as a "universal" proliferation marker and few groups have questioned the validity of the initially described reactivity, although this was tested only on very restricted experimental models. We wanted to check its reactivity on normal bone marrow (BM) samples using a multiparameter flow cytometric analysis. Although we were able to reproduce the findings of Ki-67 positivity on cultured and stimulated cells, we could not detect any convincing Ki-67 positivity on nuclei of normal BM samples. These samples all had a noticeable proliferating compartment as evidenced by their DNA content. These data are in contrast with the data we obtained starting from stressed marrows and marrows cultured in the presence of hematopoietic growth factors, where we found a marked Ki-67 positivity. This discrepancy suggests that bone marrow cells, growing and proliferating under steady-state conditions and guided by natural control mechanisms, may lose their Ki-67 expression upon exiting the progenitor compartment and entering the differentiating compartment.

Adult↗

Natural killer cell activity in Sjögren's syndrome and systemic lupus erythematosus: stimulation with interferons and interleukin-2 and correlation with immune complexes.

Natural killer (NK) cell activity and its stimulation by interferons (IFNs) and interleukin-2 (IL-2) are diminished in Sjögren's syndrome and systemic lupus erythematosus (SLE). Serum samples of these patients often contain circulating immune complexes, which may influence NK cell activity. Sixteen patients with Sjögren's syndrome (14/16 immune complex positive), 14 with SLE (9/14 immune complex positive), and 11 controls (immune complex negative) were studied. Mononuclear cells collected from a Percoll gradient were preincubated with recombinant IFN-alpha (rIFN-alpha) (100 U/ml), rIFN-gamma (1000 U/ml), rIL-2 (100 U/ml), or without cytokine. Natural killer cell activity was determined by incubating the mononuclear cells with carboxyfluorescein labelled K562 cells, and the percentage decrease of fluorescence was measured on an FACS Analyzer. In patients with Sjögren's syndrome and SLE NK cell activity and the numbers of cells expressing the NK cell associated antigens CD16 and Leu7 were diminished compared with the controls. Interleukin-2 stimulated NK cell activity significantly in comparison with the non-stimulated value in all studied groups, whereas IFN-gamma only stimulated NK cell activity in both patient groups and IFN-alpha only in patients with Sjögren's syndrome. There was no correlation between NK cell activity, with or without stimulation, and the immune complex concentrations. It is concluded that NK cell activity is decreased in Sjögren's syndrome and SLE and that it may be partially restored by IL-2 and IFN-gamma in both diseases, and by IFN-alpha in Sjögren's syndrome. The decrease of NK cell activity did not correlate with immune complex concentrations; on the other hand, decreased numbers of NK cells (CD16+ or Leu7+) and of cytokine concentrations might be important in the impaired NK cell activity in both diseases.

Antigen-Antibody Complex↗

Successful treatment of cytomegalovirus encephalitis in a patient with Hodgkin's disease in remission.

Cytomegalovirus encephalitis is a rare but life-threatening infection in non-AIDS patients. To our knowledge, no case that followed conventional treatment for Hodgkin's lymphoma has been reported. We present a patient with Hodgkin's disease in complete remission after combined modality treatment who was succesfully treated with a combination of ganciclovir and foscarnet.

Antiviral Agents↗

Cerebral complications of murine monoclonal CD3 antibody (OKT3): CT and MR findings.

Treatment of acute renal allograft rejection with mouse monoclonal antibody (OKT3) is associated with systemic and neurologic side effects. We describe cerebral abnormalities in a 13-year-old boy with steroid-resistant renal allograft rejection. After treatment with OKT3, an acute neurologic syndrome developed, including seizures, lethargy, and decreased mental function. CT and MR imaging revealed confluent cerebral lesions at the corticomedullary junction. Contrast-enhanced MR images showed patchy enhancement, indicating blood-brain barrier dysfunction. The diagnosis of OKT3-induced encephalopathy with cerebral edema and capillary leak syndrome was made. Although CT and MR findings are nonspecific, neuroradiologists should be aware of this condition in transplant patients treated with OKT3.

Adolescent↗

Adeno-associated viral vectors: background and technical aspects.

There are several obstacles that prevent the successful clinical application of gene therapy. Some of these challenges are unique to the particular disease and organ that is being targeted. Desirable characteristics of approaches aimed at delivery of a therapeutic gene to the kidney ideally will require a vector that is safe, that efficiently transduces nondividing cells, and that can lead to long-term gene expression. Viral vectors that are derived from the small replication-deficient parvovirus, adeno-associated virus, offer many potential advantages. The wild-type virus is nonpathogenic and can site specifically integrate at a single location on chromosome 19, a process that offers the hope that this characteristic could be engineered into recombinant vectors as well. Recombinant adeno-associated virus can also efficiently integrate into the host genome, can transduce nondividing cells, and does not induce an immune response which destroys the transduced cells. Efforts focused both on gaining a more complete understanding of the virus life cycle as well on the efficient production of high-titer virus should bring this vector closer to clinical application.

DNA, Recombinant↗