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J Plum

Publications and source records attributed to J Plum.

At least 19 recordsLinked to original sources
PubMed2006

T-, B- and NK-lymphoid, but not myeloid cells arise from human CD34(+)CD38(-)CD7(+) common lymphoid progenitors expressing lymphoid-specific genes.

Hematopoietic stem cells in the bone marrow (BM) give rise to all blood cells. According to the classic model of hematopoiesis, the differentiation paths leading to the myeloid and lymphoid lineages segregate early. A candidate 'common lymphoid progenitor' (CLP) has been isolated from CD34(+)CD38(-) human cord blood cells based on CD7 expression. Here, we confirm the B- and NK-differentiation potential of CD34(+)CD38(-)CD7(+) cells and show in addition that this population has strong capacity to differentiate into T cells. As CD34(+)CD38(-)CD7(+) cells are virtually devoid of myeloid differentiation potential, these cells represent true CLPs. To unravel the molecular mechanisms underlying lymphoid commitment, we performed genome-wide gene expression profiling on sorted CD34(+)CD38(-)CD7(+) and CD34(+)CD38(-)CD7(-) cells. Interestingly, lymphoid-affiliated genes were mainly upregulated in the CD7(+) population, while myeloid-specific genes were downregulated. This supports the hypothesis that lineage commitment is accompanied by the shutdown of inappropriate gene expression and the upregulation of lineage-specific genes. In addition, we identified several highly expressed genes that have not been described in hematopoiesis before.

ADP-ribosyl Cyclase 1↗
PubMed2005

Biocompatibility parameters in in-vitro simulated automated versus continuous ambulatory peritoneal dialysis.

BACKGROUND: In peritoneal dialysis, the usage of automated peritoneal dialysis (APD) has been steadily increased. As APD means larger volumes of solution and more frequent contact times with fresh dialysate, an additive negative impact on biocompatibility data, exceeding the known effect of conventional PD fluids, seems possible. For an in-vitro comparison of APD and CAPD, a new cell culture system has recently been established. METHODS: A double chamber cell culture system with human mesothelial cells on top of a permeable membrane and growth medium beyond was used for mimicking CAPD and APD. Reflecting the in vivo equilibration pattern, we compared an eight-hour CAPD with a CCPD setting, using a conventional PD solution. Cell viability was assessed with a MTT assay and cell function via constitutive and stimulated IL-6 release. CA125 was measured as a parameter of mesothelial cell integrity, and TGF-1beta was measured as an index of induction of fibrosis. RESULTS: Both the CAPD and the CCPD mode resulted in a significantly lower MTT assay and stimulated IL-6 release compared to growth medium. TGF-1beta and CA125 release did not differ between the PD modes and control. The CAPD and the CCPD mode itself did not differ with regard to MTT assay, IL-6 release, TGF-1beta and CA125 generation. CONCLUSION: From the in-vitro model imitating the acute exposure of mesothelial cells with conventional PD fluid in a CCPD and CAPD mode, there is no evidence that APD, due to the larger volumes of solution and more frequent contact times with fresh dialysate, has an acute, additive negative impact on biocompatibility parameters indicative for peritoneal host defense, mesothelial cell integrity and peritoneal fibrosis.

CA-125 Antigen↗
PubMed2003

Homeobox gene expression profile in human hematopoietic multipotent stem cells and T-cell progenitors: implications for human T-cell development.

Class I homeobox (HOX) genes comprise a large family of transcription factors that have been implicated in normal and malignant hematopoiesis. However, data on their expression or function during T-cell development is limited. Using degenerated RT-PCR and Affymetrix microarray analysis, we analyzed the expression pattern of this gene family in human multipotent stem cells from fetal liver (FL) and adult bone marrow (ABM), and in T-cell progenitors from child thymus. We show that FL and ABM stem cells are similar in terms of HOX gene expression, but significant differences were observed between these two cell types and child thymocytes. As the most immature thymocytes are derived from immigrated FL and ABM stem cells, this indicates a drastic change in HOX gene expression upon entry into the thymus. Further analysis of HOX-A7, HOX-A9, HOX-A10, and HOX-A11 expression with specific RT-PCR in all thymocyte differentiation stages showed a sequential loss of 3' region HOX-A cluster genes during intrathymic T-cell development and an unexpected expression of HOX-A11, previously not recognized to play a role in hematopoiesis. Also HOX-B3 and HOX-C4 were expressed throughout thymocyte development. Overall, these data provide novel evidence for an important role of certain HOX genes in human T-cell development.

Adult↗
PubMed2003

Successful treatment of renovascular hypertension has no effect on insulin sensitivity.

BACKGROUND: The association of insulin resistance (IR) and essential hypertension is well known, but a causal relationship has not been proven. Patients with secondary hypertension as a result of renal artery stenosis (RAS) usually do not reveal IR, but no study has addressed the effect of blood pressure reduction after successful treatment of RAS on insulin sensitivity and glucose effectiveness. PATIENTS AND METHODS: The insulin sensitivity index (SI) and glucose effectiveness (SG) were measured before and after successful intervention of an angiographically proven significant RAS in 18 out of 23 patients (eight males/10 females; mean age 51.5 +/- 13.1 years) in which improvement/cure of arterial hypertension was achieved. After a mean of 10.7 months, patients were reevaluated for 24-h blood-pressure measurement, kidney function, adrenaline, noradrenaline, plasma-renin-activity (PRA), aldosterone, atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP), and glucose metabolism parameters such as basal insulin, glucose disappearance constant (K-value), SI and SG. For calculation of SI and SG, insulin and glucose data from the modified frequent sampling intravenous glucose tolerance test (FSIGT) were submitted to the MINMOD program. RESULTS: After intervention, systolic 24-h blood pressure had decreased from 156.1 +/- 16.4 mmHg to 139.9 +/- 15.1 mmHg, and diastolic 24-h blood pressure from 97.1 +/- 14.7 mmHg to 87.3 +/- 13.4 mmHg. No significant change in SI (before 4.3 +/- 2.0, after 4.8 +/- 2.0 min(-1) per microU mL(-1)) or SG (before 1.55 +/- 0.42x10(-2) min(-1), after 1.8 +/- 0.48x10(-2) min(-1)) was observed. Aldosterone decreased from 246.7 +/- 180.7 to 115 +/- 61.4 (P=0.009) as PRA decreased from 12.4 +/- 11.4 to 4.2 +/- 7.6 ng mL h(-1) (P=0.01). Creatinine clearance, and adrenaline and noradrenaline levels as well as ANP and cGMP did not change after treatment for RAS. Subsequent to the definition of IR (SI < or =3.2x10(-4) min(-1) per microU mL(-1)) some differences among these two subgroups (SI < or =3.2, or SI>3.2) could be found. Patients with IR (n=8) were characterized by a higher body mass index (BMI), higher basal insulin values and significantly lower cGMP values. Only the group without IR (n=10) developed significant improvement of systolic blood pressure. CONCLUSION: We conclude that blood pressure reduction by treatment of RAS does not alter insulin action and that there is no link between the circulating concentrations of renin/aldosterone and glucose metabolism in renovascular hypertension (RVH). The results do not support the hypothesis of a direct link between blood pressure in RVH and the individual state of insulin sensitivity. However, patients with a normal SI are more likely to experience an almost normalization of arterial blood pressure after treatment for RAS.

Adult↗
PubMed2002

Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.

AIMS: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.

Adult↗
PubMed2002

One-compartment model for amino acids and other biological molecules in peritoneal dialysis.

OBJECTIVES: Investigation of the main factors determining the concentration-time course of amino acids and biological molecules in serum and dialysates. METHODS: In a randomized, 3-period crossover study, 11 patients were treated once with each of 3 peritoneal dialysis solutions, 1 containing amino acids and bicarbonate, 1 containing glucose and bicarbonate and 1 containing glucose and lactate. Nineteen amino acids, 3 proteins, 2 metabolites and 2 ions were measured in serum and dialysate. A standard compartment model was fitted to the data. RESULTS: The amino acids differed significantly in their kinetic characteristics (p < 0.001), mainly volume of distribution and elimination rate. Differences in absorption were small compared to the interpatient variation. The average transport rate from serum to dialysate was 0.50-1.14 h(-1), from dialysate to serum 0.33-0.41 h(-1), for elimination from the central compartment 0.35 to 2.27 h(-1), for volume of distribution 0.29 to 0.83 l/kg, for serum protein binding 19-47%, for amount in tissue 82 - 95%, for endogenous metabolic rate 16-151 micromol x kg(-1) x h(-1). The volume of distribution correlated with the R group (polar positive < aliphatic < polar uncharged). For the various proteins, the 2 bicarbonate solutions had higher serum-to-dialysate transport rates than the lactate solution (p = 0.018-0.601). CONCLUSION: The compartment model demonstrated its usefulness. Accordance with literature data for healthy volunteers indicated the validity of the estimates.

Adult↗
PubMed2002

Perioperative levels of atrial natriuretic peptide and troponin-T in patients with uncomplicated coronary artery surgery.

BACKGROUND HYPOTHESIS: increased ANP levels after uncomplicated coronary artery surgery (CAS) indicate functional reduction. METHODS EXPERIMENTAL DESIGN: prospective, randomized. Preoperative upto the 12 week postoperative. SETTING: Thoracic and Cardiovascular Surgery, University of Düsseldorf. PATIENTS: 15 patients (mean age: 58+/-6.1 years; 13 months, 2 weeks; no myocardial infarction, no congestive heart failure) with 3 vessel disease. INTERVENTIONS: levels of atrial natriuretic peptide (ANP) (pg/ml; radioimmunoassay), Troponin T (TnT) (ng/ml; ELISA test), haemodynamic parameters, ECG monitoring, m-mode echocardiography (Echo). MEASURES: increase of ANP, TnT levels during extracorporeal circulation (ECC), decrease after operation. RESULTS: Maximal increase of ANP from preoperative 90+/-10 (M+/-SEM) pg/ml (p<0.05) up to intraoperative 380+/-38 pg/ml. Ten days postoperative ANP (26+/-33 pg/ml) still threefold increased compared to preoperative level. Increasement of TnT from preoperative 0.02+/-0.01 ng/ml upto intraoperative 3.44+/-0.47 ng/ml. Ten days postoperative TnT concentration normal (0.13+/-0.11 ng/ml). Correlation of ANP and TnT five min after bypass up to 6 hrs postoperative (p<0.05, r =3.4). Increase of left atrial diameter preoperative 42.2+/-1.1 mm up to 46.8+/-1.2 mm (p<0.05) 10 days postoperative. LVEDD, EF changed from preoperative 51.1+/-0.9 mm, 73+/-2% to 54.5+/-1.2 mm, 65+/-4% 10 days postoperative. CONCLUSIONS: Threefold increase of ANP 10 days postoperative and return of TnT levels to normal under consideration of datas of echo show, that ANP is suitable to indicate the meanterm, functional, myocardial reduction. Increased ANP levels, atrial dilatation and dysfunction are important signs of cardial functional reduction after CAS.

Adult↗
PubMed2001

Enforced expression of GATA-3 severely reduces human thymic cellularity.

Following bone marrow transplantation, patients often suffer from immune incompetence by reduced or late T cell development. Moreover, adult bone marrow stem cells have a lower capacity to generate T cells compared with fetal liver- and umbilical cord blood-derived progenitors. Therefore, enhancing thymic-dependent T cell generation might hold great therapeutic potential. GATA-3 is a transcription factor that is essential in T cell development. In this study we examined the therapeutic potential of GATA-3 to enhance T cell generation by overexpressing GATA-3 in T cell progenitors followed by fetal thymic organ culture (FTOC). We observed that early during FTOC, there was an enhanced differentiation toward the double positive stage of T cell development. From day 10 of FTOC, however, overexpression of GATA-3 induced a severe reduction in thymic cellularity, which probably correlates with the absence of a functional TCR-beta chain. We further show that the frequency of apoptosis was increased in GATA-3-transduced thymocytes. Despite the absence of a functional TCR-beta chain, GATA-3 transduced progenitors were able to differentiate into CD8beta(+) double positive thymocytes. This study shows that a strictly regulated expression of GATA-3 is essential for normal T cell development and this puts severe restrictions on the potential therapeutic use of continuously overexpressed GATA-3.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2001

[Effect of cyclosporin A on renal function in patients with glomerulonephritis].

BACKGROUND AND OBJECTIVE: Cyclosporin A ( CsA) plays a confounding part in the treatment of nephrotic syndrome. Renal hemodynamics and glomerular permselectivity were investigated in patients with glomerulonephritis to analyse the antiproteinuric action of CsA and to differentiate between nephrotoxic and immunosuppressive effects. METHODS: We studied 19 patients with nephrotic syndrome after 6 months of treatment with CsA (membranous glomerulonephritis-MGN, n = 10; focal segmental sclerosing glomerulonephritis - FSGN, n = 5; minimal changes glomerulonephritis - MCGN, n = 4). Patients were studied three times within 3 weeks with (A) and without (B) CsA treatment (A-B-A'). Blood pressure, creatinine, proteinuria, C(In), C(PAH), C(Dex) were measured (analysis according to the model of Deen et al., Am J Physiol. 1985; 249 : 374). RESULTS: GFR (C (In)) increased significantly after withdrawal of CsA from 54 +/- 7.3 to 64 +/- 8.5 ml/min (p < 0.01). Proteinuria increased after withdrawal of cyclosporin (B) between 21 % (MGN) and 45 % (FSGN). After withdrawal of CsA (B) there was no change of FC(dex) in patients with MGN and FSGN. Withdrawal of CsA in patients with MCGN induced a significant decrease in glomerular selectivity in the high molecular range. CONCLUSION: These data demonstrate that CsA is able to induce even in the short term a significant increase in glomerular permselectivity in MCGN. The acute effects on GFR predominantly determined the acute antiproteinuric effects in patients with MGN and FSGN.

Adult↗
PubMed2001

Both CD34+38+ and CD34+38- cells home specifically to the bone marrow of NOD/LtSZ scid/scid mice but show different kinetics in expansion.

Human hemopoietic stem cells (HSC) have been shown to engraft, differentiate, and proliferate in the hemopoietic tissues of sublethally irradiated NOD/LtSZ scid/scid (NOD/SCID) mice. We used this model to study homing, survival, and expansion of human HSC populations from different sources or phenotype. We observed that CD34+ cells homed specifically to bone marrow (BM) and spleen, but by 3 days after injection, survived only in the BM. These BM-homed CD34+ cells proliferated intensively and gave rise to a 12-fold, 5.5-fold, and 4-fold expansion in 3 days for umbilical cord blood, adult mobilized peripheral blood, and adult BM-derived cells, respectively. By injection of purified subpopulations, it was demonstrated that both CD34+38+ and CD34+38- umbilical cord blood HSC homed to the BM and expanded. Importantly, kinetics of expansion were different: CD34+38+ cells started to increase in cell number from day 3 onwards, and by 4 wk after injection, virtually all CD34+ cells had disappeared. In contrast, CD34+38- cells remained quiescent during the first week and started to expand intensively from the third week on. In this paper, we have shown that homing, survival, and expansion of stem cells are three independent phenomena important in the early phase of BM engraftment and that kinetics of engraftment differ between CD34+38+ and CD34+38- cells.

ADP-ribosyl Cyclase↗
PubMed2001

Expression of Ly49E and CD94/NKG2 on fetal and adult NK cells.

Murine NK cells express inhibitory receptors belonging to the Ly49 and CD94/NKG2 family. Ly49E and CD94 are the only NK cell receptor transcripts detectable in fetal NK cells. Still unproved is the surface expression of Ly49E on NK cells. Here we generated two novel mAbs, a mAb recognizing Ly49E with cross-reactivity to Ly49C, and a mAb against NKG2A/C/E. Ly49E was immunoprecipitated as a disulfide-linked homodimer with 46-kDa subunits. Removal of N-linked carbohydrates revealed a 31-kDa protein backbone. NKG2A was immunoprecipitated as a 38-kDa protein. Although the frequency of fetal NK cells expressing Ly49E was higher than 25%, it decreased drastically from 2 wk after birth. Phenotypic analysis showed that approximately 90% of fetal NK cells and approximately 50% of adult NK cells express high levels of CD94/NKG2. The remaining 50% of adult NK cells expressed low surface levels of CD94/NKG2. Expression of Ly49E and CD94/NKG2 was not restricted to NK cells, but was also observed on NK T and memory T cells. Functional analysis showed that sorted Ly49E(+) and CD94/NKG2(+) fetal NK cells could discriminate between MHC class I-positive and MHC class I-negative tumor cells. We also demonstrated that Ly49E becomes phosphorylated following pervanadate stimulation of fetal NK cells. The expression levels of Ly49E and CD94/NKG2 were similar in wild-type compared with beta(2)-microglobulin(-/-) mice. In conclusion, generation of mAbs against Ly49E and NKG2 extended the phenotypic and functional characterization of NK cells.

Aging↗