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C Heilmann

Publications and source records attributed to C Heilmann.

At least 19 recordsLinked to original sources
PubMed2006

Genetic polymorphisms in the genes encoding human interleukin-7 receptor-alpha: prognostic significance in allogeneic stem cell transplantation.

Interleukin-7 (IL-7) is essential for T-cell development in the thymus and for the maintenance of peripheral T cells. IL-7 signals through IL-7R, that consists of the gammac-chain and an alpha-chain. Sequencing of IL-7Ralpha has revealed the existence of four single nucleotide polymorphisms (SNPs) (+510C/T, +1237 A/G, 2087T/C and +3110A/G), which all give rise to amino-acid substitutions. The aim of the present investigation was to evaluate the significance of IL-7Ralpha SNPs for the outcome in allogeneic stem cell transplantation (SCT). IL-7Ralpha polymorphisms were determined in 195 recipient and donor pairs from either matched sibling donors or matched unrelated donors (MUD). Genotyping of 173 normal controls was performed in parallel. In MUD transplants, the +1237 genotype of the donor was associated with survival after SCT, the mortality being highest and intermediate for the GG and AG genotypes, respectively (P = 0.023). This pattern was more pronounced with respect to treatment-related mortality (P = 0.003), while IL-7Ralpha genotypes were unrelated to the risk of relapse of leukaemia. The IL-7Ralpha +1237 genotype of the recipient and the genotypes of the other three polymorphisms, were not significantly associated with the outcome of SCT. These findings suggest that the IL-7Ralpha polymorphisms may be of importance for treatment-related mortality after SCT.

Case-Control Studies↗
PubMed2006

Differential effect of conditioning regimens on cytokine responses during allogeneic stem cell transplantation.

The purpose of this study was to characterize cytokine responses during conditioning in patients undergoing allogeneic stem cell transplantation (SCT) with the aim to identify which markers that may reliably reflect inflammatory activity during conditioning. We investigated inflammatory and anti-inflammatory mediators in plasma samples drawn daily during the conditioning of 20 patients. Soluble tumour necrosis factor alpha receptor I (sTNFRI) increased during the conditioning reflecting the type of conditioning given. Antithymocyte globulin (ATG) was the most potent inducer of sTNFRI (288% increase (median) P=0.002), followed by VP-16 (184%, P=0.03), cyclophosphamide (129%, P=0.03) and total body irradiation (148%, P=0.0005). Administration of i.v. busulfan (Busilvex; BU) was not associated with significant changes in sTNFRI levels. At day 0 (the day of stem cell infusion) the sTNFRI levels were not only elevated compared with baseline (188% increase), P<0.0001), they also correlated with the baseline values (r=0.72, P=0.0003). The levels of tumour necrosis factor, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12 stayed at low levels during the conditioning, except from a transient increase in the levels of IL-6, IL-8, IL-10 and IL- receptor antagonist (IL-Ra) seen after ATG infusion. These findings suggest that further investigation of circulating sTNFRI levels may be of interest in studies of prognostic factors in SCT.

Adult↗
PubMed2003

A comparison of T-, B- and NK-cell reconstitution following conventional or nonmyeloablative conditioning and transplantation with bone marrow or peripheral blood stem cells from human leucocyte antigen identical sibling donors.

This retrospective study compares the reconstitution of T, B and NK cells in three groups of patients transplanted for haematological malignancies with grafts from their HLA-identical sibling donors. In all, 15 patients received PBSC after a nonmyeloablative conditioning regimen consisting of fludarabine and 200 cGy TBI, 13 patients received PBSC after myeloablative conditioning and 37 patients received BM after myeloablative conditioning. In the nonmyeloablative group, the NK cells normalised after 1 month, the CD8+ T cells normalised after 3 months, the CD4+ T cells reached near normal values after 9 months and the B cell values were reduced until 12 months after transplant. In the two myeloablative groups, recipients of PBSC had a significantly higher number of CD4+ T cells after 4 months (P=0.004) and after 12 months (P=0.001), than recipients of BM. We found no differences in the T cell reconstitution between the two PBSC groups. This was of interest as the recipients of nonmyeloablative conditioning were older (P<0.001) and had a higher occurrence of chronic GVHD (P<0.05) than the recipients of myeloablative conditioning. In contrast, the recipients of nonmyeloablative conditioning had a delayed B cell recovery when compared to the patients who received myeloablative conditioning (P=0.04).

Adolescent↗
PubMed2003

Pluripotent and myeloid-committed CD34+ subsets in hematopoietic stem cell allografts.

The present study compared the contents of pluripotent and lineage-committed hematopoietic progenitor cells (HPCs) in various types of allografts. Bone marrow (BM) allografts and single leukapheresis products (LPs) collected from G-CSF-mobilized donors contained similar amounts of pluripotent HPCs (CD34(+)CD38(-)) and total CD34(+) cells. However, the content of late-myeloid HPCs (CD34(+)CD33(+)CD15(+)) were significantly higher in BM grafts compared to LPs (P>0.02), whereas the contents of early-myeloid HPCs (CD34(+)CD33(+)CD15-) were 2.5-fold higher in LPs (P<0.03). In comparison to grafts from adult donors, cord blood (CB) grafts contained 26-65-fold lower amounts of early-myeloid HPCs (P<0.001), but only 8-12-fold lower contents of pluripotent HPCs (P<0.04). Additional findings demonstrated that among all tested parameters the numbers of early-myeloid HPCs were the most accurate measure of the total colony-forming cell (CFC) numbers in allografts. Hence, the earlier engraftment observed after transplantation of LPs compared to BM grafts might be explained by the higher content of early-myeloid HPCs/CFCs in LPs. Moreover, the slow engraftment following CB transplantation might not be affected essentially by the low number of myeloid HPCs, but rather by pluripotent HPCs. Finally, this study reports a new gating strategy for the enumeration of pluripotent CD34(+)CD38(-) subsets.

Antigens, CD↗
PubMed2003

Thymic size in uninfected infants born to HIV-positive mothers and fed with pasteurized human milk.

AIM: To examine the size of the thymus in uninfected infants born to HIV-positive mothers and to study the effects of feeding by human donor milk on the size of the thymus in these infants. METHODS: The absolute and relative thymic size was assessed by sonography as thymic index (Ti), and the Ti/weight-ratio (Ti/w) at birth and at 4 mo of age in 12 healthy uninfected infants born to HlV-infected mothers. All infants were exclusively fed pasteurized donor milk. The results were compared with those obtained from a previous cohort of exclusively breastfed, partially breastfed and exclusively formula-fed infants. RESULTS: At birth the Ti was reduced in infants born to HIV-infected mothers in comparison with that in control infants but this difference disappeared when their birthweights were taken into consideration (Ti/w-ratio). At 4 mo of age the geometric mean Ti of infants fed donor milk was 23.8 and the mean Ti/w-ratio was 4.2. Compared with those of exclusively breastfed infants, the Ti and Ti/w-ratio of infants fed donor milk were significantly reduced (p < 0.01). The Ti/w-ratio increased in donor-milk-fed infants compared with that in the formula-fed infants (p = 0.02). CONCLUSION: At birth the size of the thymus was smaller in uninfected infants of HIV-positive mothers compared with infants of HIV-negative mothers but when birthweight was taken into account this difference disappeared. Feeding by human donor milk seemed to result in an increased size of the thymus at 4 mo of age compared with thymic size in infants that were exclusively formula fed.

Analysis of Variance↗
PubMed2003

Thymic size in preterm neonates: a sonographic study.

AIM: To assess the variation in size of the thymus in vivo in preterm neonates and to identify relations between thymic size and gestational age (GA), birthweight, occurrence of postnatal infections and maternal alcohol and tobacco intake during pregnancy. METHODS: Eighty preterm neonates with a GA between 24 and 36 wk, and a birthweight between 490 and 4110 g were examined between days 0 and 19 after birth. The thymic size was assessed by sonography as a volume estimate, the so-called thymic index (Ti). The median Ti was 5.2 (1.2-17.9). Ti was positively correlated with birthweight and GA and negatively correlated with occurrence of postnatal infection (p < 0.01, p = 0.03, p = 0.05, R2 = 0.68). A correlation between thymic size and maternal alcohol and tobacco intake was not demonstrated. CONCLUSION: It is possible to assess the size of the thymus by sonography in very low-birthweight and preterm neonates. A normal range for Ti in preterm neonates has been established. The sonographic method is a safe and effective technique for measuring the size of the thymus in preterm infants.

Alcohol Drinking↗
PubMed2002

Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study.

The extremely high risk reported for some types of cancer among patients with common variable immunodeficiency (CVID) is based on a limited number of investigations. Therefore, we examined the risks for cancer among 562 Danish and Swedish patients with CVID or IgA deficiency and 2071 relatives in 1958-96. The patients were identified through an Immunodeficiency Register and hospital records, while the relatives were traced through population registers. Cancer incidence was assessed by linkage to the Cancer Registries and compared with that in the general population. Among 386 patients with IgA deficiency, the incidence of cancer was not increased (standardized incidence ratio (SI) = 1.0); but two cases of stomach cancer were found, resulting in a non-significant increase in risk (SIR = 5.4; 95% CI = 0.7-19.5). Among 176 patients with common variable immunodeficiency (CVID), the incidence of cancer at all sites combined was increased (SIR = 1.8; 95% CI = 1.0-2.9), which was due mainly to significant excesses of malignant lymphoma (obs = 4; SIR = 12.1; 95% CI = 3.3-31.0) and of stomach cancer (obs = 3; SIR = 10.3; 95% CI = 2.1-30.2). Among the 626 relatives of patients with CVID, no increase in risk was found for these types of cancer or for cancer overall (obs = 53; SIR = 1.0; 95% CI = 0.8-1.3). Our data show that the risks for malignant lymphoma and stomach cancer among patients with CVID may be lower than reported previously. The absence of an increased risk among relatives suggests that the increased cancer morbidity in patients with CVID is related to the immunodeficiency per se rather than to specific genetic traits shared with their relatives.

Adult↗
PubMed2001

No disadvantage in outcome of using matched unrelated donors as compared with matched sibling donors for bone marrow transplantation in children with acute lymphoblastic leukemia in second remission.

PURPOSE: We evaluated the outcome of children with acute lymphoblastic leukemia (ALL) in second remission (2CR), comparing bone marrow transplantation (BMT) using either matched sibling donors or unrelated donors (URDs). PATIENTS AND METHODS: A total of 65 patients, aged 2 months to 20 years at BMT, with ALL in 2CR underwent allogeneic BMT at seven Nordic centers during 1990 to 1997. Of the first relapses, 85% were in bone marrow; 46% occurred on therapy, and 54%, off therapy. The preparative regimens were cyclophosphamide plus total-body irradiation +/- antithymocyte/antilymphocyte globulin, busulfan plus cyclophosphamide +/- antithymocyte/antilymphocyte globulin, or cytarabine plus total-body irradiation. Of the allografts, 37 were from HLA-matched siblings and 28 were from URDs. RESULTS: In the sibling versus URD graft recipient groups, the posttransplantation 5-year event-free survival was 39% versus 54% (P =.4), the estimated posttransplantation relapse rate was 76% versus 40% (P = not significant [NS]), and the toxic death rate was 19% versus 11% (P = NS). The incidence of significant (grade 2 to 4) acute graft-versus-host disease (GVHD) was 38% versus 64% (P <.05) and was 14% versus 32% (P <.10) for severe (grade 3 to 4) acute GVHD; the incidence of chronic GVHD was 26% versus 57% (P <.05) and was 13% versus 22% (P = NS) for extensive chronic GVHD in the sibling and URD groups. CONCLUSION: BMT with matched URD allografts offers at least equal survival for children with ALL in 2CR, as compared with allografts from matched sibling donors. URD allografts were not associated with a higher toxic mortality rate, although both acute and chronic GVHD were more frequent with URD. Indications for using matched URD allografts in ALL 2CR can be considered the same as for using matched sibling donors.

Adolescent↗
PubMed2001

Autoreactivity, backstimulation and reproducibility in a helper T lymphocyte precursor assay.

Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis (LDA) have a predictive value for alloreactivity in allogeneic bone marrow transplantation. Methodological problems in LDA include autoreactivity in the responder or stimulator cell populations and interleukin 2 (IL-2) production by the stimulator cells as a response to the responder cells (backstimulation). The extent and impact of these aspects for IL-2 production and HTLp frequency determination were studied by autologous and allogeneic mixed lymphocyte reactions with healthy volunteers and HTLp determinations from bone marrow transplantation donor/recipient pairs. We found that autoreactivity occurred in the unirradiated cells with a reproducible inter-individual variation. The immunogenicity of the stimulator cells was preserved after gamma irradiation with 50 Gy and the risks of autoreactivity and backstimulation were limited. Higher doses of irradiation decreased the immunogenicity. Immune reactions to antigens present in the serum supplement of the culture medium were seen with foetal calf serum and to a lesser extent with pooled human sera. This could be avoided by the use of autologous serum. We were unable to ensure satisfactory culture conditions in serum-free medium. The reproducibility of the HTLp frequency determinations was tested for intra- and inter-assay variation. The coefficients of variation were estimated as 24% and 35%, respectively. This was acceptable considering the range of the HTLp frequencies (1:10(2) to 1:10(7)). The influence of the extent of autoreactivity of the bone marrow donors was investigated in 28 HLA-identical sibling transplantations. We found no correlation between the autoreactivity of the donors and the HTLp frequencies. The extent of autoreactivity of the donor did not correlate with the clinical outcome in terms of acute graft-versus-host disease, treatment-related mortality, risk of relapse and overall survival. In spite of methodological difficulties and interference from autoreactivity and backstimulation, reproducible quantification of clinically significant alloreactivity can be attained.

Autoimmunity↗
PubMed2001

Characterization of the importance of Staphylococcus epidermidis autolysin and polysaccharide intercellular adhesin in the pathogenesis of intravascular catheter-associated infection in a rat model.

A rat central venous catheter (CVC) infection model was used to assess the importance of the proteinacious autolysin (AtlE) and the polysaccharide intercellular adhesin (PIA) in the pathogenesis of Staphylococcus epidermidis CVC-associated infection. Wild-type (wt) S. epidermidis O-47 was significantly more likely to cause a CVC infection than was either of the isogenic mutant strains (AtlE-negative [O-47mut1] or PIA-negative [O-47mut2]). Bacteria were retrieved from the explanted catheters of 87.5% of rats inoculated with S. epidermidis O-47, compared with 25% of rats challenged with either S. epidermidis O-47mut1 or O-47mut2 (P=.007). Peripheral bacteremia was documented in 75% of rats challenged with S. epidermidis O-47, compared with 12.5% and 25% challenged with O-47mut1 and O-47mut2, respectively (P=.009). Metastatic disease was more common in rats inoculated with wt S. epidermidis, compared with AtlE- or PIA-deficient mutants. These results confirm the importance of initial adherence, associated with AtlE, and biofilm production, mediated by PIA, in the pathogenesis of S. epidermidis experimental CVC infection.

Animals↗
PubMed2001

Teichoic acid enhances adhesion of Staphylococcus epidermidis to immobilized fibronectin.

Adhesion is a prerequisite for coagulase-negative staphylococci to cause invasive disease and may be mediated by adhesive host molecules adsorbed on implanted polymers. In this study, we can confirm previous observations demonstrating binding of Staphylococcus epidermidis to fibronectin (FN) adsorbed polymer surfaces. So far, the nature of FN-recognizing adhesin(s) in S. epidermidis remains elusive. Since teichoic acids (TA) have been shown to exert binding functions for extracellular matrix molecules in several Gram-positive species, we have purified wall TA of S. epidermidis laboratory strains KH11 and RP62A, as well as clinical isolate AB9. Using a polymethylmethacrylate (PMMA) coverslip adhesion assay, a microtitre plate assay and a particle agglutination assay, we found that purified TA significantly enhanced adhesion of S. epidermidis KH11 and RP62A to FN coated surfaces. Enhanced adhesion was dose-dependent and saturable. Preincubation, either of microorganisms or of FN coated surfaces, with TA promoted adhesion, while adhesion to TA-adsorbed PMMA was comparably low. This observation may suggest a potential role of cell wall carbohydrates as bridging molecules between microorganisms and immobilized FN in early steps of S. epidermidis pathogenesis.

Bacterial Adhesion↗
PubMed2001

Microperfusion enhancement after TMLR in chronically ischemic porcine hearts.

OBJECTIVE: The purpose of this study was to determine the effect of transmyocardial laser revascularization (TMLR) on myocardial perfusion and function in chronically ischemic myocardium. METHODS: In the first operation a stenosis of the left anterior descending artery was created in 20 open-chest anesthetized pigs to implement this ischemic model. In contrast, four pigs served as controls (thoracotomy only). Seven days later (2nd operation), all animals were studied at baseline by analyzing different parameters of perfusion (radioactive microspheres), function, and intramyocardial pressure. Afterwards, pigs who received a left anterior descending artery stenosis were randomized into one of three groups: animals in laser group 1 (n=7) received one and in laser group 2 (n=7) two laser channels per cm(2) in the left anterior descending artery territory. Animals of the ischemic group (n=6) underwent the same procedures without transmyocardial laser revascularization. Three months later, the animals were re-studied (3rd operation) and additional analysis of histochemistry and myocardial water content was performed. RESULTS: Regional myocardial blood flow (RMBF) in laser group 2 revealed statistically higher RMBF values compared to the ischemic group (0.39+/-0.13 versus 0.14+/-0.12 ml/min/g; P=0.043), after 3 months, whereas the absolute RMBF had not increased compared to the 1-week baseline values. Left ventricular stroke work index (LVSWI) at rest and under stress did not show any improvement compared to the initial values in all study groups (P=ns). Nevertheless, laser group 1 demonstrated relatively higher LVSWI(max) values compared to the ischemic (1.33+/-0.19 versus 0.93+/-0.16 mJ/kg; P=0.03) and laser group 2 (1.33+/-0.19 versus 1.02+/-0.15; P=0.024). Regional contractility of laser groups 1 and 2 recovered after 3 months (which had deteriorated shortly after transmyocardial laser revascularization) and increased under stress (100% versus 144.33+/-46.42, P=0.029 and 100% versus 116.26+/-21.06, P=0.034; respectively). In contrast, the corresponding ischemic group values were not different from initial values (P=ns). CONCLUSIONS: This model of chronic regional ischemia demonstrates that CO(2)-laser revascularization significantly improves microperfusion and regional function, whereas the overall perfusion and global LV function is unchanged.

Angioplasty, Laser↗
PubMed2001

The predictive value of helper T lymphocyte precursor frequencies for graft-versus-host disease and graft-versus-leukaemia effects in allogeneic bone marrow transplantation.

Helper T lymphocyte precursor (HTLp) frequencies determined by limiting dilution analysis were studied in the graft-versus-host direction to assess the predictive value for outcome in allogeneic BMT. The HTLp frequencies correlated with the degree of HLA disparity. HTLp frequencies from 28 HLA-identical sibling BMT pairs had a median of 1:557 362 (range 1:9511 to <1:2 500 000). The HTLp frequencies from 20 HLA-matched unrelated and partially HLA-matched related BMT pairs had a median of 1:88 110 (range 1:4139-1:736 123). The HLA-identical sibling BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:500 000. There was a trend towards a higher risk for acute GVHD > or =grade II (P = 0.075) in the high frequency group. There was no difference in TRM. The high HTLp frequency group had a significantly higher risk for chronic GVHD (P = 0.04), a significantly lower risk for relapse (P = 0.01), as well as a significantly better overall survival (P = 0.045) and leukaemia-free survival (P = 0.008). The HLA-matched unrelated and partially HLA-matched related BMT pairs were split evenly into high and low HTLp frequency groups above and below 1:90 000. There was a significantly higher risk for acute GVHD > or = grade II (P = 0.007) in the high HTLp frequency group. There was a trend towards a higher TRM in the high HTLp frequency group (P = 0.05). There were no differences in chronic GVHD, risk of relapse, overall survival and leukaemia-free survival. Analyzing all 48 patients the risk of acute GVHD > or = grade II and TRM was significantly higher (P = 0.012 and 0.021, respectively) with HTLp frequencies >1:100 000 and there was a trend towards a higher risk of relapse (P = 0.058) with low HTLp frequencies <1:400 000. Patients in the intermediate HTLp frequency group 1:100 000-1:400 000 had a trend towards improved survival (P = 0.059). The HTLp frequency seems to detect clinically significant differences in alloreactivity, that can be useful in donor selection and graft engineering.

Adolescent↗
PubMed2001

Flow cytometric assessment of lymphocyte subsets, lymphoid progenitors, and hematopoietic stem cells in allogeneic stem cell grafts.

Currently, bone marrow (BM), cord blood (CB), and G-CSF-mobilized peripheral blood progenitor cells (PBPCs) are the most commonly used sources for allogeneic stem cell transplantation (SCT). The aim of this study was to assess the yields and distribution of lymphocyte subsets, lymphocyte progenitors and hematopoietic stem cells (HSC) in each type of allograft by three-color flow cytometry. The yields of CD34(+)CD38(-) HSCs did not differ significantly between BM grafts (2.80 +/- 0.74 x 10(6)) and leukapheresis products (LPs) (1.82 +/- 0.64 x 10(6)), and were lowest in CB grafts (0.21 +/- 0.05 x 10(6)). For most lymphocyte subsets yields were lowest in CB grafts and significantly higher in LPs than in BM grafts. BM grafts, however, contained the highest yields of CD34(+)CD19(+)CD20(-) B cell progenitors and CD19(+)CD20(-) B cells. The relative frequencies of the naive CD45RA(+)CD45RO(-) phenotype among CD4(+) and CD8(high) T cells were highest in CB grafts (P < or = 0.001), and higher in LPs than in BM grafts (P < or = 0.02). The latter finding was in accordance with a preferential G-CSF mobilization of naive T cells relative to the total lymphocyte population (P < or = 0.014). CD3(+)CD8(low) and CD3(+)CD8(low)CD4(-) subsets, which facilitate engraftment in murine transplantation models, demonstrated a tendency towards lower frequencies among T cells in CB grafts and LPs compared to BM grafts. This observation coincided with a significantly reduced mobilization of subsets potentially enriched for facilitating cells as compared to the total lymphocyte population (P < or = 0.036). The CD34(+) compartment of CB grafts contained a significantly higher percentage (12.1%) of CD34(+)CD7(+)CD3(-) T cell progenitors than those of BM grafts (5.1%) and LPs (3.6%). In addition, CB lymphocytes contained the highest fraction of CD3(-)CD16/56(+) NK cells (P < or = 0.013) and almost no CD3(+)CD16/56(+) NKT cells (P < 0.001) compared to adult cell sources. In summary, LPs, CB allografts and BM allografts differ widely with respect to the cellular composition of their lymphocyte compartments, which is partially affected by a varying mobilization efficiency of G-CSF for distinct lymphocyte subsets.

Adult↗
PubMed2001

Treatment of resistant mycoplasma infection in immunocompromised patients with a new pleuromutilin antibiotic.

Patients with primary antibody deficiency (PAD) are prone to mycoplasma infection with unusual strains which may be resistant to conventional antibiotics. Mycoplasmas were isolated from the joint fluid (Ureaplasma urealyticum) of two PAD patients with arthritis and from the cerebral spinal fluid (Mycoplasma maculosum) in one with meningitis, the latter probably originating from the patient's dog. Combinations of doxycycline and quinolones or macrolides failed to clear the infections, but after demonstrating in-vitro sensitivity to the pleuromutilin, Econor, for two of the isolates, all three patients responded to oral treatment with Econor. The infection was completely eradicated in two patients, with the emergence of a resistant strain in the third. Mycoplasma infection should be considered in PAD patients with unexplained sepsis. Pleuromutilins such as Econor are powerful new anti-mycoplasmal agents which provide an additional therapeutic option when patients fail to respond to conventional antibiotics.

Adolescent↗
PubMed2001

Proteome analysis of interleukin-1beta--induced changes in protein expression in rat islets of Langerhans.

The intracellular molecular events involved in the beta-cell death process are complex but poorly understood. Cytokines, e.g., interleukin (IL)-1beta, may play a crucial role in inducing this process. Protein synthesis is necessary for the deleterious effect of IL-1, and induction of both protective and deleterious proteins has been described. To characterize the rather complex pattern of islet protein expression in rat islets in response to IL-1, we have attempted to identify proteins of altered expression level after IL-1 exposure by 2D gel electrophoresis and mass spectrometry. Of 105 significantly changed (i.e., up- or downregulated or de novo-induced) protein spots, we obtained positive protein identification for 60 protein spots. The 60 identifications corresponded to 57 different proteins. Of these, 10 proteins were present in two to four spots, suggesting that posttranslatory modifications had occurred. In addition, 11 spots contained more than one protein. The proteins could be classified according to their function into the following groups: 1) energy transduction; 2) glycolytic pathway; 3) protein synthesis, chaperones, and protein folding; and 4) signal transduction, regulation, differentiation, and apoptosis. In conclusion, valuable information about the molecular mechanisms involved in cytokine-mediated beta-cell destruction was obtained by this approach.

Animals↗
PubMed2000

Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation.

Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429)

Adolescent↗