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Biomedical subjects

D Stachel

Publications and source records attributed to D Stachel.

14 recordsLinked to original sources
PubMed2006

Bone marrow Th2 cytokine expression as predictor for relapse in childhood acute lymphoblastic leukemia (ALL).

The immunological environment of leukemic blasts in the bone marrow might play a decisive role in determining an individual's risk for relapse. In order to identify potential predictors of relapse and to elucidate the mechanisms of immune control of leukemic blasts we examined the expression of cytokines, costimulatory molecules and members of the TNF family in leukemic marrow samples in a prospective study. Samples from 49 consecutive pediatric patients with B cell precursor acute lymphocytic leukemia (BCP ALL) were analyzed by semiquantitative RT-PCR. We identified interleukin (IL)-10 expression as a significant adverse prognostic indicator in childhood BCP-ALL. The event free survival (EFS) of patients expressing IL-10 mRNA in high quantity was significantly lower compared with patients expressing low IL-10 mRNA. Taqman RT-PCR of sorted cell populations showed that IL-10 mRNA was synthetized almost exclusively by NK or T cells. In addition, we found an increased expression of IL-1, IL-4, CD86 and VEGF mRNA in patients with late relapses. Possibly, ALL cells mediate a Th2 shift through increased expression of CD86 and thereby influence the individual relapse risk. These findings emphasize the role of the immune system for the outcome of childhood ALL.

Adolescent↗
PubMed2005

Local environment and dynamics of PO4 tetrahedra in Na-Al-PO3 glasses and melts.

Glasses and melts in the system (NaPO3)(1-x)(Al(PO3)3)x were studied with the aim of obtaining information about the structure on the next larger scale beyond the PO4 group. Magic angle spinning NMR was applied to the pure NaPO3 glass and Raman scattering to systems with x = 0.00, 0.03, 0.06, 0.15, and 0.60 in the temperature range T = 300-1100 K. Comparison of the 31P chemical shift between glass and crystalline forms revealed that polymerization of the metaphosphate into tricyclophosphatelike (PO3)3(3-) rings is the dominant structure, ca. 80%, formed by the twofold vertex-joined PO4 groups in the glass. In the Raman study we focused on the prominent polarized band at ca. 1170 cm(-1) which is due to the symmetric breathing mode of the tetrahedral PO4 group. This band was decomposed into a few Gaussian lines. These component lines could be identified using the NMR results: two narrow components are due to PO4 groups in the tricyclophosphatelike rings, which have either a Na or an Al counterion and a third broad component is due to chain-polymerized (PO3(-))n. The variations of the component lines (peak positions, widths, and intensities) with respect to x and T are presented. We derive the shifts of the symmetric breathing mode frequency which are caused by Na or Al counterions, by ring closure, by x > 0, etc. The relative intensities of the narrow and broad components in the 1170-cm(-1) band of the Raman spectra are discussed. The amount of ring-to-chain transformation on addition of Al3+, and as functions of T and x, is derived. Indications for ordering on a next larger scale, derivable from Raman, NMR, and thermodynamics, are compared.

Journal Article↗
PubMed2001

Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children.

We performed HLA-mismatched stem cell transplantation with megadoses of purified positively selected mobilized peripheral blood CD34(+) progenitor cells (PBPC) from related adult donors in 39 children lacking an otherwise suitable donor. The patients received a mean number of 20.7 +/- 9.8 x 10(6)/kg purified CD34(+) and a mean number of 15.5 +/- 20.4 x 10(3)/kg CD3(+) T lymphocytes. The first seven patients received short term (<4 weeks) GVHD prophylaxis with cyclosporin A, whereas in all the following 32 patients no GVHD prophylaxis was used. In 38 evaluable patients, five patients experienced primary acute GVHD grade I and one patient grade II. In 32 patients, no signs of primary GVHD were seen and GVHD only occurred after T cell add backs. T cell reconstitution was more rapid if the number of transplanted CD34(+) cells exceeded 20 x 10(6)/kg. Of the 39 patients, 15 are alive and well, 13 died due to relapse and 10 transplant-related deaths occurred. We conclude that the HLA barrier can be overcome by transplantation of megadoses of highly purified mismatched CD34(+) stem cells. GVHD can be prevented without pharmacological immunosuppression by the efficient T cell depletion associated with the CD34(+) positive selection procedure. This approach offers a promising therapeutic option for every child without an otherwise suitable donor.

Adolescent↗
PubMed1998

Cryopreservation and transplantation of fetal adrenal glands in adrenalectomized rats.

In a syngeneic rat model, the present study investigated the cryobiology of fetal adrenal glands and compared the endocrinological function of cryopreserved versus fresh fetal adrenal transplants in the adrenalectomized hosts. Ultrastructural studies showed no significant tissue damage by the cryopreserving technique: cellular membranes were intact, the mitochondria showed discrete swelling and vacuoles were found in the endoplasmatic reticulum. Following transplantation, maturation and bilateral adrenalectomy in the host, assessment of endocrinological parameters demonstrated that survival was prolonged and Addison crisis could be prevented in both transplant groups with no significant difference between fresh versus cryopreserved grafts. To our knowledge this study presents the first morphological and endocrinological data about the successful transplantation of cryopreserved fetal adrenal glands in rats. In conclusion, cryopreservation is tolerated well by the tissue and long-term banking may therefore contribute to the feasibility and benefit of fetal adrenal transplantation. However, further investigations will be necessary to evaluate fetal adrenal transplantation in an allogeneic and xenogeneic setting.

Adrenal Glands↗
PubMed1995

Allogenic peripheral blood stem cell (PBSC) transplantation in two patients with graft failure.

Allogenic peripheral blood stem cells (PBSC) were used for graft failure after BMT in two patients. These PBSC were mobilized by G-CSF in the same donors, harvested and given without reconditioning to the patients. In one patient, PBSC with a very high T cell number were given unprocessed, in the other patient, CD34+ cells were positively enriched due to a 2-antigen difference. None of the patients had hyperacute GVHD. Trilineage engraftment was seen after 13 days. Acute GVHD grade II to III developed on days +31 in patient 1 and +16 in patient 2, involving predominantly gut and liver, but sparing the skin. Thus, allogeneic PBSCT for graft failure did not cause hyperacute GVHD even with very high T cell numbers in patient 1, and graft failure with CD34 selected PBSC was successfully reversed even with a low number of T cells in patient 2.

Adolescent↗
PubMed1992

Cytomegalovirus and marrow function.

Infection with cytomegalovirus (CMV) continues to be one of the most common complications following allogeneic bone marrow transplantation. A proportion of patients with CMV infection also experience neutropenia. To investigate the possible role of CMV in the suppression of hematopoiesis, we have examined the effect of CMV on the growth of isolated myeloid progenitors and on the production of myeloid cells in the long-term bone marrow culture (LTMC) system. In these studies, various isolates of CMV were added either directly to cultures of progenitors or to LTMC established from normal CMV-seronegative donors. In the first system, myelosuppression is manifested by a reduction in the number of colonies that grow. In the second system, myelosuppression is manifested by a reduction in the number of myeloid cells produced and released into the culture supernatant. Analysis of the data observed indicated that myelosuppression could in some cases be attributed to direct infection of myeloid progenitors. In other cases stromal cells were infected. In the latter cases, myelosuppression was then caused by an alteration in cytokines produced by the stromal cells. These observations made in vitro raise the possibility that comparable mechanisms may be responsible for the myelosuppression observed with CMV infection in vivo. To pursue this possibility we proposed to detect the CMV genome in defined subpopulations of marrow cells isolated from infected patients. Given the technical restrictions imposed by the small sample size available from patient marrow aspirations, our initial attempts to develop on appropriate technique involved isolation of cells from CMV-seropositive normal bone marrow donors. Using the polymerase chain reaction we were able to amplify CMV DNA contained within marrow cells of some healthy CMV-seropositive marrow donors.

Bone Marrow↗
PubMed1988

Class II (DR) antigen expression on CD8+ lymphocyte subsets in acquired immune deficiency syndrome (AIDS).

In a selected group of human immunodeficiency virus (HIV)-infected patients we confirm the expansion of a CD8+ T-lymphocyte subset, i.e., the CD8+/Leu7+ cells, which account for 30% of the lymphocytes, compared to 3% in the control donors. In addition, a CD8+ T-lymphocyte subset that coexpresses class II (DR) antigens, i.e., CD8+/DR+ cells, is also increased from 1.5% in controls to 27% in the HIV-infected patients. Using three-color immunofluorescence and flow cytometry we can demonstrate that the CD8+/Leu7+ and the CD8+/class II+ cells are not distinct but overlapping subsets. In the HIV-infected patients 42% of the CD8+/Leu7+ cells were strongly positive for class II and these CD8+/Leu7+/class II+ cells accounted for 13% of all lymphocytes. These findings indicate that the expanded CD8+/Leu7+ cells are activated and hence might be actively involved in immune defense in acquired immune deficiency syndrome (AIDS).

AIDS-Related Complex↗
PubMed1985

Expansion of a minor subpopulation of peripheral blood lymphocytes (T8+/Leu 7+) in patients with haemophilia.

Immunological analysis of peripheral blood mononuclear cells (PBM) was performed in 20 patients with haemophilia A or B. One of the patients had never received clotting factor substitution in his life. Six different sources of lyophilized clotting factor were used for the other patients, but every given patient received factor from one source, exclusively. None of the patients exhibited lymphadenopathy and only one suffered from local bacterial infection. Mononuclear cell counts were within the normal range and mitogen stimulation with phythaemagglutinin (PHA) and concanavalin A (Con A) was found normal in all but two patients. Ratios of helper and suppressor cells (T4/T8) were below 1.0 in 10 of the patients. Some of these patients had a relative increase of T8+ cells and at the same time of Leu 7+ (natural killer (NK)/suppressor) cells. Double-marker analysis revealed that the subpopulation of cells expressing both the T8 and the Leu 7 antigen, which on the average accounted for 2.1% of the mononuclear cells in controls, was increased 4.5 fold (9.1%) in haemophilia patients. One patient exhibited 37.8% T8+/Leu 7+ double-marker cells. VEP13+ cells (active NK cells) were decreased below the normal range in 11 of the patients. Abnormal values for lymphocyte subsets were found in every treatment group. The patient who had never received any clotting factor exhibited normal values in all respects. In an additional set of patients, those with increased percentage of T8+/Leu 7+ cells exhibited decreased NK cell activity indicating that the T8+/Leu 7+ cells are not active NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Accelerated phase in partial albinism with immunodeficiency (Griscelli syndrome): genetics and stem cell transplantation in a 2-month-old girl.

UNLABELLED: A 2-month-old girl presented with fever, hepatosplenomegaly, pancytopenia, hypertriglyceridaemia and silvery-greyish hair, suggesting the diagnosis of Griscelli syndrome (partial albinism with immunodeficiency). This diagnosis was confirmed by the characteristic agglomeration of melanin in the hair shaft and accumulation of melanosomes in melanocytes of the skin. The patient was homozygous for polymorphic markers around the myosin-Va gene on chromosome 15q21, which co-localize to the Griscelli disease locus. Natural-killer cells were in the lower range. The stimulation of lymphocytes with antigen and mitogen was normal. The patient's accelerated phase, characterized by haemophagocytosis was treated with prednisolone, rabbit anti-thymocyte globulins, and intrathecal methotrexate. Remission was maintained with cyclosporin A until HLA-compatible peripheral blood stem cell transplantation from her mother. CONCLUSION: The silvery-greyish hair associated with fever, pancytopenia and hypertriglyceridaemia is the clue to early diagnosis of Griscelli syndrome and important to prevent death before stem cell transplantation.

Chromosomes, Human, Pair 15↗
PubMedDate not supplied

Pamidronate and calcitonin as therapy of acute cancer-related hypercalcemia in children.

Severe symptomatic hypercalcemia is a rare event in children with malignancies. Up to now there is limited experience treating childhood hypercalcemia with bisphosphonates in addition to calcitonin. We report a 5-year-old boy with acute lymphoblastic lymphoma who presented with malignant hypercalcemia at diagnosis. The maximal serum calcium concentration was 15.2 mg/dl (3.81 mmol/l). Conventional therapy with forced diuresis and furosemide failed. Calcitonin (10 IU/kg/24 h i.v. for 2 days) and pamidronate (1 mg/kg over 2 hours i.v.) were used successfully without adverse effect lowering the serum calcium level within 24 hours to normal values. We recommend the use of calcitonin and pamidronate as first-line therapy together with forced diuresis and furosemide in childhood hypercalcemia secondary to malignancies as it is rapidly effective and has no significant side effects.

Alkaline Phosphatase↗
PubMedDate not supplied

[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature].

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Brain Neoplasms↗