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Biomedical subjects

M Herrmann

Publications and source records attributed to M Herrmann.

At least 73 records · Page 4Linked to original sources
PubMed2000

Treatment with annexin V increases immunogenicity of apoptotic human T-cells in Balb/c mice.

Exposure of phosphatidylserine on the outer leaflet of the cytoplasmic membrane is an early event during apoptotic cell death and serves as a recognition signal for phagocytes. Usually the clearance of apoptotic cells does not initiate inflammation or immune response. We investigated the immune response in Balb/c mice towards apoptotic human T-cells. Animals injected with apoptotic cells showed significantly reduced humoral immune responses, especially Th1-dependent IgG2a titres, compared to controls immunised with viable cells. However, treatment of apoptotic cells with annexin V (AxV) significantly increased the humoral immune response. AxV binds with high affinity to anionic phospholipids and as a result interferes with the phosphatidylserine recognition by phagocytes. Our results indicate that AxV treatment may be used to increase the efficiency of apoptotic cell-based vaccines, e.g. some tumour vaccines.

Animals↗
PubMed2000

Mercury induces cell cytotoxicity and oxidative stress and increases beta-amyloid secretion and tau phosphorylation in SHSY5Y neuroblastoma cells.

Concentrations of heavy metals, including mercury, have been shown to be altered in the brain and body fluids of Alzheimer's disease (AD) patients. To explore potential pathophysiological mechanisms we used an in vitro model system (SHSY5Y neuroblastoma cells) and investigated the effects of inorganic mercury (HgCl2) on oxidative stress, cell cytotoxicity, beta-amyloid production, and tau phosphorylation. We demonstrated that exposure of cells to 50 microg/L (180 nM) HgCl2 for 30 min induces a 30% reduction in cellular glutathione (GSH) levels (n = 13, p<0.001). Preincubation of cells for 30 min with 1 microM melatonin or premixing melatonin and HgCl2 appeared to protect cells from the mercury-induced GSH loss. Similarly, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that 50 microg/L HgCl2 for 24 h produced a 50% inhibition of MTT reduction (n = 9, p<0.001). Again, melatonin preincubation protected cells from the deleterious effects of mercury, resulting in MTT reduction equaling control levels. The release of beta-amyloid peptide (Abeta) 1-40 and 1-42 into cell culture supernatants after exposure to HgCl2 was shown to be different: Abeta 1-40 showed maximal (15.3 ng/ml) release after 4 h, whereas Abeta 1-42 showed maximal (9.3 ng/ml) release after 6 h of exposure to mercury compared with untreated controls (n = 9, p<0.001). Preincubation of cells with melatonin resulted in an attenuation of Abeta 1-40 and Abeta 1-42 release. Tau phosphorylation was significantly increased in the presence of mercury (n = 9, p<0.001), whereas melatonin preincubation reduced the phosphorylation to control values. These results indicate that mercury may play a role in pathophysiological mechanisms of AD.

Amyloid beta-Peptides↗
PubMed2000

Dominant T cells in idiopathic nephrotic syndrome of childhood.

BACKGROUND: Because of several studies, idiopathic nephrotic syndrome (INS) of childhood is suspected to have an immunologic pathogenesis with T cells playing a major role. To investigate this hypothesis further, we studied the diversity of the CDR3 region of the T-cell receptor (TCR) beta-chain from peripheral T cells isolated from patients with INS. METHODS: The study was performed over a three-year period to obtain longitudinal data on the repertoire of peripheral T cells. mRNA from peripheral mononuclear cells (PBMCs) of seven INS patients and two healthy controls (NHD) was prepared and analyzed for CDR3 length polymorphism of TCR beta-chain by spectratyping. RESULTS: All INS patients presented individually skewed spectratype histograms in at least one Vbeta-family. Patients suffering from a frequent relapsing course of INS or a focal global sclerosis showed some alterations to persist in all samples isolated in the observation period (up to 3 years). In addition, sequence analyses of the beta-chain of the TCR CDR3 region confirmed clonal expansion of peripheral T cells in those patients who had displayed spectratype alterations. CONCLUSIONS: The data give strong evidence for an direct involvement of CD8+ T cells in the complicated course of INS.

Age of Onset↗
PubMed2000

[Neuropsychological deficits in depressive disorders].

Neuropsychological deficits are considered a significant feature of depression both for their differential value in the diagnostics and the underlying pathophysiology of depressive disorders. The studies reviewed in the present paper predominantly focus on memory disorders as well as frontal-lobe associated dysfunctions such as deficits of attentional performance and executive functions. Despite heterogeneous results in the literature, there is emerging evidence that executive functions and anterograde memory performance are those domains predominantly affected in depressive disorders. The fact that not all depressive patients display neuropsychological deficits rather indicates a dominant role of moderating variables. We discuss the following variables possibly intervening with type and degree of neuropsychological dysfunction: [1] severity and remission of depressive disorders, [2] age of patients and age at the first manifestation of a depressive disorder, [3] psychological factors such as motivation and coping with failure, [4] type and efficacy of antidepressive drug treatment, [5] duration of the stay as inpatients, [6] number of depressive episodes, and [7] gender. Furthermore, we discuss the theory of a dysfunction of fronto-striatal circuits as an underlying mechanism of depressive disorders. The majority of neuropsychological findings seem to support this theory.

Attention↗
PubMed2000

UVB-irradiated T-cells undergoing apoptosis lose L-selectin by metalloprotese-mediated shedding.

PURPOSE: L-selectin (CD62L) is a prerequisite for leucocyte adhesion to endothelial cells of blood vessels and consequently for transmigration. Its expression on the cell surface therefore regulates the ability of lymphocytes to enter lymph nodes, to re-enter blood vessels or to invade tissues at sites of inflammation. The aim of this study was to determine the expression of CD62L on apoptotic lymphocytes after UVB irradiation. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of normal healthy volunteers. Cells were stimulated with phorbol myristate acetate (PMA) and ionomycin for activation. Apoptosis in peripheral T-cells and Jurkat cells was induced by irradiation with UVB (120 mJ/cm2). In addition, T-cells or Jurkat cells were cultured for the indicated time with anti-Fas antibody CH11. The CH11-induced apoptosis was inhibited by the pan-caspase inhibitor zVAD-fmk. For detection of apoptosis, cells were analysed by cytofluorometry for morphological changes typical for apoptosis. The reliability of the apoptotic cell gate was confirmed by staining with FITC-labelled annexin-V in the presence ofpropidium iodide (PI). For FACS analysis of CD62L expression on the cell-surface immunofluorescence was performed using FITC-conjugated anti-CD62L and PE-conjugated anti-CD3 antibodies. Soluble CD62L (sCD62L) in the cell supernatants was measured by standard ELISA technique. Assays were performed in the presence and absence of metalloprotease inhibitor KB8301. RESULTS: PBMC from healthy volunteers undergoing apoptosis following UVB irradiation selectively shed CD62L, whereas the expression of the lineage-specific marker CD3 showed only minor changes. Shedding was blocked by the hydroxamic acid-based metalloprotease inhibitor KB8301. When Jurkat cells were treated with the caspase inhibitor zVAD-fmk, anti-CD95 antibodies did not induce apoptosis, and the expression of CD62L remained unaltered. CONCLUSION: UVB or ionizing radiation induce apoptosis in lymphocytes. The loss of CD62L is associated with apoptosis and will influence lymphocyte trafficking and, by excluding them from CD62L-mediated adhesion and tissue invasion, might contribute to the regulation of inflammation.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Temporal profile of release of neurobiochemical markers of brain damage after traumatic brain injury is associated with intracranial pathology as demonstrated in cranial computerized tomography.

This study aimed at the investigation of release patterns of neuron specific enolase (NSE) and protein S-100B after traumatic brain injury (TBI) and their association with intracranial pathologic changes as demonstrated in computerized tomography (CT). We analyzed NSE and S-100B concentrations in serial venous blood samples taken one to three days after TBI in 66 patients by the use of immunoluminometric assays. These markers are considered to be specific neurobiochemical indicators of damage to glial (S-100B) or neuronal (NSE) brain tissue. Standardized neurological examination and plani- and volumetric evaluation of computerized tomography scans were performed in all patients. Patients with medium severe to severe TBI [Glasgow Coma Scale (GCS) score at the site of accident < or =12] exhibited significantly higher NSE and S-100B concentrations and a significantly longer release compared to patients with minor head injury (GCS: 13-15). Both, patients with and without visible intracerebral pathology in CT scans exhibited elevated concentrations of NSE and S-100B after TBI and a significant decrease in the follow-up blood samples. Release patterns of S-100B and NSE differed in patients with primary cortical contusions, diffuse axonal injury (DAI), and signs of cerebral edema (ICP) without focal mass lesions. All serum concentrations of NSE and S-100B were significantly correlated with the volume of contusions. The data of the present study indicate that the early release patterns of NSE and S-100 may mirror different pathophysiological consequences of traumatic brain injury.

Adolescent↗
PubMed2000

Bactericidal effect of extracorporeal shock waves on Staphylococcus aureus.

Despite considerable knowledge about the effects of shock waves on eukaryotic soft tissues, no data are available concerning their effect on prokaryotic micro-organisms. In vitro studies on the bactericidal effect of extracorporeal shock waves on staphylococci were performed with energy levels that are standard for the disintegration of calculi. Suspensions containing 10(4)-10(5) cfu of Staphylococcus aureus/ml were sealed in plastic tubes and exposed to shock waves, resulting in a mean decrease of 3.1 log(10). Whereas impulse rates of > or =350 resulted in a decrease of cfu/ml equalling the detection limit, lower numbers of impulses did not result in an appreciable bactericidal effect. The bactericidal effect of extracorporeal shock waves might provide the basis for the development of novel therapeutic strategies for bacterial infections.

Lithotripsy↗
PubMed2000

Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells.

Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin alpha(5)beta(1) (B. Sinha et al., Cell. Microbiol. 1:101-117, 1999). However, it is unknown whether this mechanism is sufficient for S. aureus invasion. To address this question, various S. aureus adhesins (FnBPA, FnBPB, and clumping factor [ClfA]) were expressed in Staphylococcus carnosus and Lactococcus lactis subsp. cremoris. Both noninvasive gram-positive microorganisms are genetically distinct from S. aureus, lack any known S. aureus surface protein, and do not bind fibronectin. Transformants of S. carnosus and L. lactis harboring plasmids coding for various S. aureus surface proteins (FnBPA, FnBPB, and ClfA) functionally expressed adhesins (as determined by bacterial clumping in plasma, specific latex agglutination, Western ligand blotting, and binding to immobilized and soluble fibronectin). FnBPA or FnBPB but not of ClfA conferred invasiveness to S. carnosus and L. lactis. Invasion of 293 cells by transformants was comparable to that of strongly invasive S. aureus strain Cowan 1. Binding of soluble and immobilized fibronectin paralleled invasiveness, demonstrating that the amount of accessible surface FnBPs is rate limiting. Thus, S. aureus FnBPs confer invasiveness to noninvasive, apathogenic gram-positive cocci. Furthermore, FnBP-coated polystyrene beads were internalized by 293 cells, demonstrating that FnBPs are sufficient for invasion of host cells without the need for (S. aureus-specific) coreceptors.

Adhesins, Bacterial↗
PubMed2000

Staphylococcus aureus RN6390 replicates and induces apoptosis in a pulmonary epithelial cell line.

Staphylococcus aureus frequently colonizes the airways of patients with compromised airway defenses (e.g., cystic fibrosis [CF] patients) for extended periods. Persistent and relapsing infections may be related to live S. aureus bacteria actively residing inside epithelial cells. In this study, we infected a respiratory epithelial cell line, which was derived from a CF patient, with S. aureus RN6390. Internalization of S. aureus was found to be time and dose dependent and could be blocked by cytochalasin D. Transmission electron microscopy revealed that internalized bacteria resided within endocytic vacuoles without any evidence of lysosomal fusion in a 24-h period. The results of internalization experiments and time-lapse fluorescence microscopy of epithelial cells infected with green fluorescent S. aureus indicate that, after an initial lag period of 7 to 9 h, intracellular bacteria began to replicate, with three to five divisions in a 24-h period, leading to apoptosis of infected cells. Induction of apoptosis required bacterial internalization and is associated with intracellular replication. The slow and gradual replication of S. aureus inside epithelial cells hints at the role of host factors or signals in bacterial growth and further suggests possible cross talk between host cells and S. aureus.

Apoptosis↗
PubMed2000

Etiopathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus is an autoimmune disease of unknown etiology. Research efforts of the last few years have mainly focused on basic molecular and cellular pathogenetic processes of the disease. Consequently, this paper reviews the etiopathogenetic hallmarks, such as impaired amount and presentation of nuclear antigens, production of antinuclear antibodies by T-cell-dependent B cell stimulation and organ damage by anti-dsDNA antibodies or immune complexes that are discussed at the present time. In summary, the hypothesis of a dysregulation of apoptotic cell clearance is strongly supported and broadly discussed.

Animals↗
PubMed2000

Release of glial tissue-specific proteins after acute stroke: A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein.

BACKGROUND AND PURPOSE: This study was aimed at the comparative analysis of serum concentrations of glial fibrillary acidic protein (GFAP) and protein S-100B in patients with acute stroke. METHODS: We investigated 32 patients with stroke symptoms consistent with cerebral ischemia in the anterior territory of vascular supply. Serial venous blood samples were taken after admission to the hospital and during the first 4 days after onset of stroke. Evaluation of lesion topography and volume of infarcted brain area was based on cranial CT data. The patients' clinical status was consecutively evaluated by the National Institutes of Health Stroke Scale (NIHSS) and the Barthel Index score at discharge from the hospital. RESULTS: Protein S-100B and GFAP release was found to be significantly correlated (r=0.96; P:<0.001). The release of both biochemical markers was associated with the volume of brain lesions (S-100B: r=0.957, P:<0.0001; GFAP: r=0.955, P:<0.0001) and the neurological status at discharge from the hospital (S-100B: r=0.821, P:=0.0002; GFAP: r=0.717, P:=0.0003). The highest correlation between both S-100B and GFAP serum concentration and Barthel score was calculated at the last time of blood sampling, 4 days after stroke onset (S-100B: r=0.621, P:<0.001; GFAP: r=0.655, P:<0.001). The release of both astroglia derived proteins differed between different subtypes of stroke. GFAP was found to be a more sensitive marker of brain damage in patients with smaller lacunar lesions or minor strokes. CONCLUSIONS: Our results indicate that postischemic release patterns of GFAP and S-100B protein may allow insight into the underlying pathophysiology of acute cerebral infarcts and may be used as a valuable tool of clinical stroke treatment.

Acute Disease↗
PubMed2000

Neurobehavioral outcome prediction after cardiac surgery: role of neurobiochemical markers of damage to neuronal and glial brain tissue.

BACKGROUND AND PURPOSE: The goal of the present study was to investigate the predictive value of neurobiochemical markers of brain damage (protein S-100B and neuron-specific enolase [NSE]) with respect to the short- and long-term neuropsychological outcomes after cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We investigated 74 patients who underwent elective CABG or valve replacement surgery and who showed no severe neurological deficits after surgery. Patients were investigated with a standardized neurological examination and a comprehensive neuropsychological and neuropsychiatric assessment 1 to 2 days before surgery, 3 and 8 days after surgery, and 6 months later. Serial venous blood samples were taken preoperatively and 1, 6, 20, and 30 hours after skin closure. Protein S-100B and NSE were analyzed with immunoluminometric assays. RESULTS: Patients with severe postoperative neuropsychological disorders showed a significantly higher and longer release of neurobiochemical markers of brain damage. Patients who presented with a delirium according to DSM-III-R criteria 3 days after surgery had significantly higher postoperative S-100B serum concentrations. Multivariate analysis (based on postoperative NSE and S-100B concentrations and age of patients, type of operation, length of cross-clamp and perfusion time, and intraoperative and postoperative oxygenation) identified NSE and S-100B concentrations 6 to 30 hours after skin closure as the only variables that contributed significantly to a predictive model of the neuropsychological outcome. NSE, but not S-100B, release was significantly higher in patients undergoing valve replacement surgery. CONCLUSIONS: Postoperative serum concentrations and kinetics of S-100B and NSE have a high predictive value with respect to the early neuropsychological and neuropsychiatric outcome after cardiac surgery. The analysis of NSE and S-100B release might allow insight into the underlying pathophysiology of brain dysfunction, thus providing a valuable tool to monitor and evaluate measures to improve cardiac surgery with CPB.

Biomarkers↗
PubMed2000

In the search for specific inhibitors of human 11beta-hydroxysteroid-dehydrogenases (11beta-HSDs): chenodeoxycholic acid selectively inhibits 11beta-HSD-I.

OBJECTIVE: Selective inhibitors of 11beta-hydroxysteroid-dehydrogenase type I may be of therapeutical interest for two reasons: i) 9alpha-Fluorinated 11-dehydrosteroids like 11-dehydro-dexamethasone (DH-D) are rapidly activated by human kidney 11beta-hydroxysteroid-dehydrogenase type II (11beta-HSD-II) to dexamethasone (D). If the same reaction by hepatic 11beta-HSD-I could be selectively inhibited, DH-D could be used for selective renal immunosuppressive therapy. ii) Reduction of cortisone to cortisol in the liver may increase insulin resistance in type 2 diabetes mellitus, and inhibition of the enzyme may lead to a decrease in gluconeogenesis. Therefore, we characterized the metabolism of DH-D by human hepatic 11beta-HSD-I and tried to find a selective inhibitor of this isoenzyme. METHODS: For kinetic analysis of 11beta-HSD-I, we used microsomes prepared from unaffected parts of liver segments, resected because of hepatocarcinoma or metastatic disease. For inhibition experiments, we also tested 11beta-HSD-II activity with human kidney cortex microsomes. The inhibitory potency of several compounds was evaluated for oxidation and reduction in concentrations from 10(-9) to 10(-5)mol/l. RESULTS: Whereas D was not oxidized by human liver microsomes at all, cortisol was oxidized to cortisone with a maximum velocity (V(max)) of 95pmol/mg per min. The reduction of DH-D to D (V(max)=742pmol/mg per min, Michaelis--Menten constant (K(m))=1.6 micromol/l) was faster than that of cortisone to cortisol (V(max)=187pmol/mg per min). All reactions tested in liver microsomes showed the characteristics of 11beta-HSD-I: K(m) values in the micromolar range, preferred cosubstrate NADP(H), no product inhibition. Of the substances tested for inhibition of 11beta-HSD-I and -II, chenodeoxycholic acid was the only one that selectively inhibited 11beta-HSD-I (IC(50) for reduction: 2.8x10(-6)mol/l, IC(50) for oxidation: 4.4x10(-6)mol/l), whereas ketoconazole preferentially inhibited oxidation and reduction reactions catalyzed by 11beta-HSD-II. Metyrapone, which is reduced to metyrapol by hepatic 11beta-HSD-I, inhibited steroid reductase activity of 11beta-HSD-I and -II and oxidative activity of 11beta-HSD-II. These findings can be explained by substrate competition for reductase reactions and by product inhibition of the oxidation, which is a well-known characteristic of 11beta-HSD-II. CONCLUSIONS: Our in vitro results may offer a new concept for renal glucocorticoid targeting. Oral administration of small amounts of DH-D (low substrate affinity for 11beta-HSD-I) in combination with chenodeoxycholic acid (selective inhibition of 11beta-HSD-I) may prevent hepatic first pass reduction of DH-D, thus allowing selective activation of DH-D to D by the high affinity 11beta-HSD-II in the kidney. Moreover, selective inhibitors of the hepatic 11beta-HSD-I, like chenodeoxycholic acid, may become useful in the therapy of patients with hepatic insulin resistance including diabetes mellitus type II, because cortisol enhances gluconeogenesis.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Childhood experiences and adult behavior in a group of women with pain accounted for by psychological factors and a group recovered from major depression.

OBJECTIVE: In this study twenty-four women with pain accounted for by psychological factors (DSM-IV, 307.80) and twenty-four with major depression diagnosed according to DSM-III-R were compared to study the relationship between pain and depression. METHOD: They were examined by a semi-structured, tape-recorded interview to study their childhood experiences and adult behavior. The interviews were rated by two independent and blind raters. Interrater correlation (Cohen-Kappa) varied between good and close agreement. RESULTS: Of childhood experiences, "brutality between parents," "brutality toward child," and "sexual abuse" were often found in both groups and were more strongly represented in these than in comparison groups of former studies. As adults, the pain group had experienced more serious illness (p = 0.037) and surgery (p = 0.014). The depression group more often had a history of depression (15/24 vs. 4/24; p = 0.001). The pain group spoke negatively of its physicians (p = 0.001), was more hostile during the interview (p = 0.041), was less convinced of the benefit of the hospital stay (p = 0.029), felt less self-responsible, and was more pessimistic (p = 0.013). The pain patients also provoked negative emotions in the raters, whereas the latter's reaction to the depression group was compassion and interest (p = 0.0005) (Pearson's chi2 and Fisher's exact tests). CONCLUSIONS: The results show that negative childhood experiences are prominent and similar in patients with pain accounted for by psychological factors and in patients after major depression. Adult behavior, however, is very different.

Adult↗
PubMed1999

Vitronectin interaction with glycosaminoglycans. Kinetics, structural determinants, and role in binding to endothelial cells.

Vitronectin (VN) is a high affinity heparin-binding protein. The physiological role of this binding has hitherto received little attention, and its molecular determinants are subject to controversy. In this study, we characterized vitronectin interaction with heparin, heparin analogues, bacterial extracts, and cell surface glycosaminoglycans. As assessed by (i) fluorescence assays, (ii) precipitation with heparin-Sepharose beads, or (iii) Western blotting with antibodies against VN(347-361) (the heparin-binding site), we demonstrate an exposure of the VN heparin-binding site in multimeric but not monomeric vitronectin. Through its heparin-binding site, vitronectin also bound other glycosaminoglycans and Staphylococcus aureus extracts. The kinetics of heparin binding to vitronectin were complex. After a fast association phase (tau = 0.3 s), a slow conversion of an unstable to a stable heparin-vitronectin complex (tau = 180 s) occurred. Heparin binding kinetics and transition to a stable complex were mimicked by VN(347-361), demonstrating that this area is the fully functional heparin-binding site of vitronectin. Multimeric vitronectin bound to endothelial cells. This binding was blocked by soluble heparin and was not observed when endothelial cells were pretreated with glycosaminoglycan-removing enzymes. Glycosaminoglycan-dependent interaction of endothelial cells with multimeric vitronectin might be a relevant mechanism for removal of multimeric vitronectin from plasma. Conversion of an unstable to a stable glycosaminoglycan-vitronectin complex is likely to be relevant for association with endothelial cells under flow conditions.

Cells, Cultured↗
PubMed1999

Kinetic study of CD34+ cells during peripheral blood stem cell collections.

The impact of the separated volume on the yield of CD34+ cells during peripheral blood stem cell collections (PBSCC) remains controversial. We therefore studied the CD34+ cell concentration in the peripheral blood of patients (pts) during PBSCC as well as the total amount of CD34+ cells collected after each blood volume (BV) processed and engraftment data for each cycle of high dose chemotherapy (HD Ctx). A total of 21 PBSCC from 20 patients with different malignancies were analyzed. Stem cells were mobilized by chemotherapy and G-CSF (14 pts) or GM-CSF (6 pts). Samples from the pts peripheral blood and the collection bag were taken after each BV processed and analyzed for CD34+ cells, WBC, platelets (plt), and hemoglobin (Hb). The total volume processed was two to five times the pts calculated BV (mean value 17.4 L, range 9.0-24.0 L). Sixteen pts could be evaluated for engraftment. The mean peripheral blood CD34+ cell count was 116+/-103.5/microl at the start of PBSCC and decreased to 57+/-61.6/microl after processing of four times the pts BV. The mean number of CD34+ cells collected after each BV was 2.3+/-2.4, 5.8+/-5.2, 8.5+/-7.2, and 11.8+/-10.3x10(6) per kg body weight, respectively. The mean plt count decreased by 53+/-40.2/nl, Hb by 1.+/-0.5 g/dl and WBC by 0.+/-6.1/nl after separation of 4 BV. All but two pts reached the target value of 1.5x10(6) CD34+ cells/kg body weight and planned cycle of HD Ctx with 1 PBSCC. All pts engrafted and reached neutrophils>500/microl and plt>20,000/microl at a median of 11 and 13 days, respectively. We could demonstrate, that the yield of CD34+ cells during PBSCC increased continuously with the volume of the separated BV and that up to 5x the patients' BV could be processed safely without serious side effects. Most pts had to undergo only 1 PBSCC to collect sufficient numbers of CD34+ cells to support sequential courses of HD Ctx without delayed engraftment.

Adult↗